Human Serum Albumin (HSA), a major protein in blood plasma, exhibits pseudo-enzymatic activity such as pseudo-esterase activity. This study explores the impact of glycation on the pseudo-esterase activity of HSA. Glycation, a non-enzymatic reaction between reducing sugars and HSA was induced using glucose, fructose, and ribose. Glycated HSA samples (gHSA, fHSA, and rHSA) were analyzed for their pseudo-esterase activity using p-nitrophenyl acetate (PNPA) as a substrate. The kinetics of the enzyme-substrate reaction were studied, and structural changes monitored through UV-Vis, fluorescence, and circular dichroism (CD) spectroscopy. Glycation was confirmed using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-ToF) mass spectrometry. Results indicated a significant reduction in the pseudo-esterase activity of glycated HSA compared to native HSA. Ribose-induced glycation exhibited the highest reduction in activity, attributed to the higher glycation efficiency of ribose. Fluorescence studies revealed changes in Trp fluorescence, suggesting conformational alterations in glycated as well as acetylated HSA. CD spectroscopy confirmed secondary structural changes upon glycation, followed by acetylation. A binding study was conducted to deduce the effect of glycation and acetylation of HSA on its binding activity. These findings highlight the significance of understanding how glycation modifies the biochemical properties of HSA, impacting its physiological roles and therapeutic applications in metabolic disorders. Our studies specifically reveal that glycation impairs the pseudo-esterase activity and alters the drug-binding properties of HSA.

The aims of this study were to compare the metabolic profiles of type 2 diabetes mellitus patients with metformin and insulin monotherapy, to assess the associations of metabolites with major adverse cardiovascular events (MACE) distinctly for metformin-only and insulin-only users, and to test for effect modification by the glucose-lowering treatment.

We included 3,058 metformin-only and 558 insulin-only users from the UK Biobank. Mean concentrations of 249 metabolites of metformin and insulin users were compared with Cohen's d, their associations with MACE were assessed with Cox regression and interaction terms were tested.

Mean VLDL size, HDL size, and concentrations of large and very large HDL molecules differed between insulin-only and metformin-only users. Overall, 75 metabolomic biomarkers were significantly associated with MACE in insulin-only users and 57 in metformin-only users. Significant interaction terms were observed between treatment group and albumin (protective in metformin users only) and 86 lipids/fatty acids, which were all statistically significantly associated with MACE among insulin users only.

Metformin and insulin users have different metabolic profiles and a consistent pattern emerged that the metabolic profile of metformin users is favorable compared to the one of insulin users due to a lower associated MACE risk.

Zwitterions consisting of positively and negatively charged groups confer hydrophilicity while retaining overall charge neutrality. Both properties were identified as decisive prerequisites for protein-resistant coatings. In this work, we studied the electrostatic contributions to the bacterial attachment process by altering the interfacial charge distribution of the two charges and correlated the results with bacterial adhesion data. Therefore, we generated a set of well-defined, quasi-zwitterionic, charge-equilibrated self-assembled monolayers on gold-coated substrates. As cationic component (11-mercaptoundecyl)-N,N,N-trimethylammonium was combined in a 1:1 ratio with anionic thiols of varying alkyl spacer lengths. By embedding 8-mercaptooctanoic acid, 12-mercaptododecanoic acid, or 16-mercaptohexadecanoic acid, the distance of the anionic moiety to the surface could be varied while maintaining the distance of the cationic moiety to the substrate. Thereby, the interfacial charge distribution and thus the average orientation of the zwitterionic dipoles of the charge-equilibrated mixed self-assembled monolayers have been systematically varied. The resistance against the nonspecific adsorption of the blood-related proteins human serum albumin and fibronectin as well as the attachment-inhibiting effect against the pathogenic bacteria Escherichia coli, Pseudomonas fluorescens, and Bacillus subtilis was tested. It turned out that the change in dipole orientation affected the proteins and the bacteria in different ways with an equilibrated charge distribution within the surface plane being in total the superior one. The results are further discussed based on streaming current data revealing net surface charge of the self-assembled monolayers and the apparent zeta potential of the bacteria to understand to what degree electrostatic interactions contribute to the attachment process.

Elemental impurities in drug products may pose a risk to patient health. Therefore, maintaining the levels of these impurities below certain limits is essential for patient safety. Human albumin solution, one of the parenteral drugs used for many years, is crucial in various treatments. Also, the European Pharmacopoeia specifies limits for potassium, aluminum, and sodium in this drug. Inductively coupled plasma-atomic absorption spectrometry (ICP-AAS) and ICP-optical emission spectrometry (ICP-OES) are used for detecting elemental impurities. However, neither method can simultaneously analyze all three impurities within the pharmacopeial limits. This study aimed to develop a new method for simultaneously detecting the levels of potassium, aluminum, and sodium in human albumin-based drugs using ICP-mass spectrometry (ICP-MS). The limit of detection (LOD), specificity, linearity, repeatability, and accuracy were examined, and the recovery percentage was calculated. For Na, K, and Al elements, detection limits were calculated as 0.0105767 μg/mL, 0.001748 μg/mL, and 2.0568E - 4 μg/mL, respectively. Precision and reliability of this method have been proven by the linearity regression coefficients that were found as 0.999, 0.999, and 0.995 for Na, K, and Al. In addition, repeatability recovery rates were 98.70%, 98.38%, and 90.83%; accuracy analysis results were 101.45%, 94.53%, and 108.83% for 50% level; 98.26%, 93.93%, and 95.83% for 100% level; 100.48%, 95.90%, and 107.22% for 150% level for Na, K, and Al elements, respectively. This study successfully developed and validated ICP-MS for the simultaneous quantitative determination of the levels of potassium, aluminum, and sodium in human albumin solution.

Albumin, the most abundant protein, contributes significantly to various physiological processes, indicating its multifunctional properties. It has drawn the attention of scientists and physicians because of its primary role in maintaining osmotic pressure and involvement in transporting numerous small molecules, including hormones, fatty acids, and drugs. A growing body of evidence has recently illustrated an additional aspect of albumin's antioxidant properties. Therefore, based on recent research findings, this review article delves into the molecular and biochemical aspects of albumin's antioxidative capabilities. We highlight the multifaceted significance of proteins in oxidative stress and their relation to pathologies in obstetrics and gynecology. In particular, we focused on preeclampsia, in which oxidative stress is closely involved in the pathogenesis, and renal dysfunction leads to increased albumin excretion into the urine, resulting in hypoalbuminemia. In addition, we discussed the role of albumin in preeclampsia pathogenesis, diagnosis, and patient prognosis. Understanding the antioxidant properties of albumin opens new avenues for therapeutic intervention and sheds light on novel strategies for combating preeclampsia associated with oxidative damage. In this study, we employed the PubMed database to search for articles that assessed the antioxidant properties of albumin, with a specific focus on obstetric diseases, particularly preeclampsia. The last update of the search was conducted in November 2024.

The partition coefficient of human serum albumin (HSA) was analyzed in the PEG600-Dex70, 0.15 M NaCl/KCl in 0.01 M Na/K phosphate buffer, pH 7.4 aqueous two-phase system, with varying concentrations of ten different drugs: caffeine, cefmetazole, oxacillin, propranolol, theophylline, verapamil, warfarin, atenolol, diltiazem, and terbutaline. All the drugs were found to increase HSA's partition coefficient, but they affected its behavior differently. We empirically determined that an exponential equation could describe the dependence of the partition coefficient for each drug. Notably, we observed a correlation between the drug's clearance times in the human body and the parameters of the exponential equation. This suggests a link between the efficiency of drug clearance from the bloodstream and the conformational changes in HSA, induced by its interaction with the drug, and the characteristics of partitioning the resulting HSA-drug complex in the aqueous two-phase system.

Human serum albumin (HSA), a crucial plasma protein, plays a significant role in drug interactions within the bloodstream, bearing considerable clinical relevance. Bortezomib (BTZ) is a potent anti-cancer drug for multiple myeloma (MM) and mantle cell lymphoma (MC). The mechanism of BTZ transfer in the blood remains undetermined. This study aims to investigate the binding of BTZ to HSA using the techniques of differential scanning calorimetry (DSC), circular dichroism (CD), fluorescence spectroscopy, and computational methods such as molecular docking and molecular dynamics simulations. This study presents the thermal dissection of domain I (DI) of HSA by subjecting it to a temperature elevation of 79.2 °C (2 °C above Tm of DI) using DSC, which provides new information on the thermal behavior of HSA domains. Furthermore, the deconvolution analysis of the HSA thermogram in the absence and presence of BTZ revealed that the drug binding site is located in DI and impacts DII. The interaction between BTZ and HSA with a binding affinity (Kb) of 7.744±0.2 ×105 M-1 influences protein dynamics and reduces HSA's thermal stability by almost 1 °C. This study is crucial for predicting the pharmacokinetics and pharmacodynamics of BTZ, aiding in developing safer and more effective treatments for MM and MC.

Cancer immunotherapy remains a low immune response rate in clinic because of dominant immunosuppressive tumor microenvironment (TME) and lack of effective drug to specifically remodel the TME. In this work, we introduced a tumor-seeking human serum albumin (HSA) based delivery platform by covalently conjugating with a tumor-targeting near-infrared (NIR) photosensitizer (IR-DBI) and non-covalently loading of immune modulator Resiquimod (R848). HSA exhibited tumor-preferential accumulation after covalent conjugation with IR-DBI. Meanwhile, HSA restricted the rotation of IR-DBI, narrowed the HOMO-LUMO energy gap, significantly enhanced fluorescent intensity and dual-modal phototherapy (PTT/PDT). The enhanced phototherapeutic effect further induced robust ICD effect. More importantly, non-covalent loading of R848 could be released from HSA at tumor sites by laser irradiation-induced heat. The in-situ release of R848 in TME efficiently promoted the maturation of DC cells and repolarized M2 macrophages to M1 macrophages. Consequently, robust photo-induced antitumor immunity was triggered in the different mice models bearing primary and distant tumors or lung metastasis, which was further enhanced by combining with CTLA-4 blockade therapy. Taken together, this work may present a versatile albumin composite which exhibits tumor-preferential accumulation and imaging-guided PDT/PTT/immunotherapy.

Acute liver failure (ALF) is a rare syndrome where rapid deterioration of liver function occurs after an acute insult in a patient without prior chronic liver disease and leads to jaundice, hepatic encephalopathy (HE), and oftentimes multiorgan failure (MOF). At this time, the only definitive treatment for ALF is LT but some patients, particularly APAP-induced ALF patients, may have ongoing regenerative capacity of the liver and may not require LT with ongoing supportive management. As a result, extracorporeal liver support (ECLS) has been a topic of interest both as a bridge to LT and as a bridge to spontaneous recovery and aims to remove damaging toxins that further aggravate liver failure, stimulate regeneration of the liver, and improve pathophysiologic consequences of liver failure. There are currently two categories of ECLS (artificial and bioartificial). Artificial ECLS does not incorporate active hepatocytes and are based on the principles of filtration and adsorption and includes renal replacement therapy (RRT), plasma adsorption including plasma exchange and Prometheus (Fractionated Plasma Separation and Adsorption), and albumin dialysis including MARS (Molecular Adsorbent Recirculating System) and SPAD (Single Pass Albumin Dialysis). Bioartificial ECLS incorporates active hepatocytes (human or porcine in origin) to improve liver detoxification capacity and to support hepatic synthetic function and includes ELAD (Extracorporeal Liver Assist Device) and HepatAssist.

Albumin (ALB) has numerous vital physiological outcomes for healthy aging. A decrease in serum albumin, i.e., hypoalbuminemia, is one of the risk factors associated with aging, which affects physiological functioning. Hypoalbuminemia is the outcome of either decreased ALB synthesis or increased degradation. However, the potential mechanism controlling ALB's mRNA level expression in aged individuals is yet to be explored. We noted decreased serum ALB concentrations in aged individuals participating in our study, as compared to the young ones. We found that IL-10, a paradoxical inflammaging marker, reduced ALB concentration in HepG2 cells. Inhibiting the JAK/STAT3 signalling increased albumin mRNA suggesting its IL-10-driven regulation via JAK/STAT3 pathway. Albumin promotor analysis revealed the presence of a CEBP-β binding site. We showed that CEBP-β binds to the albumin promoter in an IL-10-dependent manner. Further, IL-10 increased the expressions of all CEBP-β isoforms, including the inhibitory isoform (LIP). The CEBP-β inhibition either by a functional inhibitor (i.e., quercetin) or shRNA silencing increased albumin mRNA in HepG2 cells. Our finding showed that IL-10 likely regulates albumin expression in a JAK/STAT3 and CEBP-β dependent manner in aging. A better understanding of the underlying condition can improve albumin protein levels and the well-being of the aged population.

Nowadays, it is largely accepted that albumin should not be used in hypoalbuminemia or for nutritional purpose. The most discussed indication of albumin at present is the resuscitation in shock states, especially distributive shocks such as septic shock. The main evidence-based indication is also liver disease. In this review, we provided updated evidence-based instruction for definite and potential indications of albumin administration in clinical practice, with appropriate dosing and duration.

Data collection was carried out until November 2023 by search of electronic databases including PubMed, Google Scholar, Scopus, and Web of Science. GRADE system has been used to determine the quality of evidence and strength of recommendations for each albumin indication.

A total of 165 relevant studies were included in this review. Fluid replacement in plasmapheresis and liver diseases, including hepatorenal syndrome, spontaneous bacterial peritonitis, and large-volume paracentesis, have a moderate to high quality of evidence and a strong recommendation for administering albumin. Moreover, albumin is used as a second-line and adjunctive to crystalloids for fluid resuscitation in hypovolemic shock, sepsis and septic shock, severe burns, toxic epidermal necrolysis, intradialytic hypotension, ovarian hyperstimulation syndrome, major surgery, non-traumatic brain injury, extracorporeal membrane oxygenation, acute respiratory distress syndrome, and severe and refractory edema with hypoalbuminemia has a low to moderate quality of evidence and weak recommendation to use. Also, in modest volume paracentesis, severe hyponatremia in cirrhosis has a low to moderate quality of evidence and a weak recommendation.

Albumin administration is most indicated in management of cirrhosis complications. Fluid resuscitation or treatment of severe and refractory edema, especially in patients with hypoalbuminemia and not responding to other treatments, is another rational use for albumin. Implementation of evidence-based guidelines in hospitals can be an effective measure to reduce inappropriate uses of albumin.

The fouling resistance of zwitterionic coatings is conventionally explained by the strong hydrophilicity of such polymers. Here, the in vitro biocompatibility of a set of systematically varied amphiphilic, zwitterionic copolymers is investigated. Photocrosslinkable, amphiphilic copolymers containing hydrophilic sulfobetaine methacrylate (SPe) and butyl methacrylate (BMA) were systematically synthesized in different ratios (50:50, 70:30, and 90:10) with a fixed content of photo-crosslinker by free radical copolymerization. The copolymers were spin-coated onto substrates and subsequently photocured by UV irradiation. Pure pBMA and pSPe as well as the prepared amphiphilic copolymers showed BMA content-dependent wettability in the dry state, but overall hydrophilic properties a fortiori in aqueous conditions. All polysulfobetaine-containing copolymers showed high resistance against non-specific adsorption (NSA) of proteins, platelet adhesion, thrombocyte activation, and bacterial accumulation. In some cases, the amphiphilic coatings even outperformed the purely hydrophilic pSPe coatings.

Renal fibrosis is the result of all chronic kidney diseases and is becoming a major global health hazard. Currently, traditional treatments for renal fibrosis are difficult to meet clinical needs due to shortcomings such as poor efficacy or highly toxic side effects. Therefore, therapeutic strategies that target the kidneys are needed to overcome these shortcomings. Drug delivery can be attained by improving drug stability and addressing controlled release and targeted delivery of drugs in the delivery category. By combining drug delivery technology with nanosystems, controlled drug release and biodistribution can be achieved, enhancing therapeutic efficacy and reducing toxic cross-wise effects. This review discusses nanomaterial drug delivery strategies reported in recent years. Firstly, the present review describes the mechanisms of renal fibrosis and anti-renal fibrosis drug delivery. Secondly, different nanomaterial drug delivery strategies for the treatment of renal injury and fibrosis are highlighted. Finally, the limitations of these strategies are also discussed. Investigating various anti-renal fibrosis drug delivery strategies reveals the characteristics and therapeutic effects of various novel nanosystem-derived drug delivery approaches. This will serve as a reference for future research on drug delivery strategies for renal fibrosis treatment.

Serum cholinesterase (ChE) levels are considered to reflect nutritional status. Although ChE has been well documented as a prognostic factor for some cancers, no clear consensus on its use for colorectal cancer (CRC) has been reached. The aim of this study was to investigate the relationship between preoperative serum ChE and postoperative long-term prognosis in CRC patients.

A total of 1053 CRC patients who underwent curative surgery were included in this study. The correlations between the preoperative ChE value and overall survival (OS) or cancer-specific survival (CSS) were assessed. By dividing patients into two groups according to their ChE value, OS and CSS were compared between the groups.

Multivariate analysis revealed that the continuous ChE value was a significant predictor of OS (hazard ratio, 0.996; 95% CI, 0.993-0.998; p = 0.002) and CSS (hazard ratio, 0.994; 95% CI, 0.991-0.998; p = 0.001), independent of other variables. The low-ChE (≤234 U/L) group had a significantly poorer prognosis than the high-ChE (>234 U/L) group for both OS (5-year OS for low ChE and high ChE: 79.8% and 93.3%, respectively; p < 0.001) and CSS (5-year CSS for low ChE and high ChE: 84.8% and 95.6%, respectively; p < 0.001).

Lower preoperative serum ChE levels are a predictive factor of poor prognosis for CRC patients. As serum ChE levels can be measured quickly and evaluated easily, ChE could become a useful marker for predicting the postoperative long-term outcomes of CRC patients.

Bariatric surgery is an effective treatment for severe obesity, but complications and peri-operative monitoring are important considerations. We conducted a comprehensive review of studies assessing pre-operative biomarkers and complications in patients undergoing bariatric surgery. A total of 14 studies were included. Gastric leak, infections, bleeding, obstruction or stenosis, hypoglycemia, and hypoalbuminemia were the most common complications observed. Our analysis showed a significant association between lower pre-operative albumin levels and complications (SMD [95%CI] =  - 0.21 [- 0.38; - 0.04]). However, other biomarkers did not have a significant impact on complication occurrence. Changes in C-reactive protein, neutrophil-lymphocyte ratio, and white blood cell levels were observed in certain peri-operative time points and complication subgroups. These findings suggest the potential use of pre-operative biomarkers and peri-operative changes of biomarker's levels for predicting complications.

In this study, we report a small molecule optical marker BI-CyG derived from the structural engineering of a cyanine scaffold. The developed probe offers suitable advantages over existing cyanine-based albumin specific probes in terms of its excitation and emission wavelengths, which are 760 and 830-832 nm, respectively. Structural tuning of the cyanine architecture leading to extended π-conjugation and resulting in a suitable bathochromic shift in the emission wavelength of the probe is represented in this study. The probe besides emitting in the NIR region, also possesses the desirable characteristics of being a potential target selective optical marker, as established from various biophysical studies. Molecular modelling and simulation studies provided critical insights into the binding of the probe in the protein microenvironment, which was further supported by experimental studies. The probe displayed intracellular albumin selectivity and was utilized for demonstrating alteration in albumin levels in pathological states such as hyperglycemia in hepatic cells. The present study also sheds some light on using BI-CyG as an imaging probe and on the role of metformin as a suitable drug for balancing hyperglycemia-induced reduced intra-hepatic albumin levels. The study, thus, attempts to highlight the structural derivatization of cyanine to afford a potential probe for serum albumin and its deployment to image altering albumin levels in an induced pathological condition, hyperglycemia.

Albumin, a key protein in human blood plasma, has been linked to various health conditions. However, its association with malaria, particularly in assessing disease severity, remains inadequately understood. This comprehensive systematic review and meta-analysis aimed to elucidate the relationship between albumin levels and malaria severity. A comprehensive literature search was conducted across multiple databases, including Embase, Scopus, PubMed, MEDLINE, Ovid, and Google Scholar, to identify studies examining albumin levels in malaria patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Data were pooled using a random-effects model, and heterogeneity was assessed using I2 statistics. Subgroup and meta-regression analyses were performed based on publication year, study location, and Plasmodium species. A total of 37 studies were included in this review. The thematic synthesis indicated that albumin levels in malaria patients varied significantly based on geographical location. A meta-analysis of 28 studies found that albumin levels were significantly lower in malaria patients compared with non-malarial controls (P < 0.001, standardized mean differences [SMD] = -2.23, 95% CI - 3.25 to - 1.20, I2: 98%, random effects model, 28 studies). Additionally, subgroup analysis revealed variations in albumin levels based on geographical location and Plasmodium species. Regarding the association with disease severity, thematic synthesis showed that severe malaria cases generally had decreased albumin levels across various regions. However, one Brazilian study reported higher albumin levels in severe cases. A separate meta-analysis of five studies found significantly lower albumin levels in patients experiencing severe malaria relative to those with less severe forms of the disease (P < 0.001, SMD = -0.66, 95% CI - 1.07 to - 0.25), I2: 73%, random effects model, 5 studies). This study underscores the clinical significance of albumin as a potential biomarker for Plasmodium infection and the severity of malaria. The findings suggest that albumin level monitoring could be crucial in managing malaria patients, especially in assessing disease severity and tailoring treatment approaches. Additional studies are required to investigate the underlying mechanisms driving these associations and validate the clinical utility of albumin levels in malaria patient management.

Venous thromboembolism (VTE) in critically ill patients has been well-studied in Western countries. Many studies have developed risk assessments and established pharmacological protocols to prevent deep venous thrombosis (DVT). However, the DVT rate and need for pharmacologic VTE prophylaxis in critically ill Taiwanese patients are limited. This study aimed to prospectively determine the DVT incidence, risk factors, and outcomes in critically ill Taiwanese patients who do not receive pharmacologic VTE prophylaxis.

We conducted a prospective study in a surgical intensive care unit (SICU) of a tertiary academic medical center in Taiwan. Adult patients admitted to SICU from March 2021 to June 2022 received proximal lower extremities DVT surveillance with venous duplex ultrasound. No patient received pharmacologic VTE prophylaxis. The outcomes were the incidence and risk factors of DVT.

Among 501 enrolled SICU patients, 21 patients (4.2%) were diagnosed with proximal lower extremities DVT. In a multivariate regression analysis, hypoalbuminemia (odd ratio (OR) = 6.061, 95% confidence interval (CI): 1.067-34.421), femoral central venous catheter (OR = 4.515, 95% CI: 1.547-13.174), ICU stays more than 10 days (OR = 4.017, 95% CI: 1.270-12.707), and swollen leg (OR = 3.427, 95% CI: 1.075-10.930) were independent risk factors for DVT. In addition, patients with proximal lower extremities DVT have more extended ventilator days (p = 0.045) and ICU stays (p = 0.044).

Our findings indicate critically ill Taiwanese patients have a higher incidence of DVT than results from prior retrospective studies in the Asian population. Physicians who care for this population should consider the specific risk factors for DVT and prescribe pharmacologic prophylaxis in high-risk groups.

Albumin is the most abundant protein in human serum and a specific amount of albumin also can be found in the saliva. It has several physiological functions such as blood colloidal osmotic pressure, antioxidant activity, binding and transporting of endogenous and exogenous substrates. We conducted an electronic search across several databases such as PubMed, Scopus, Cochrane, Embase and Science Direct using the relevant MeSH terms and keywords like "albumin", "serum albumin", "salivary albumin", "oral health" "dental caries" and "epidemiology". Only the epidemiological studies published between 2010 and 2023 were included. After the application of the inclusion criteria, a total of 51 studied were included in this narrative review. Serum and salivary albumin tests have been used in various aspects of oral health as a diagnostic and prognostic factor. Some of the results point out to a pattern of association while some of them are inconclusive and even contradictory. This narrative review discusses the role, significance and impact of albumin in epidemiological oral health related studies including the categories of periodontal health and disease, dental caries, oral function and hypofunction, nutrition and malnutrition, tooth loss and its treatment, diabetes and cancer. In addition, it offers a short manual for the researchers on when, where and how to use albumin tests in planning their study designs whether investigating an association or measure them as a covariate.

To examine the association of lactate-to-albumin ratio (LAR) with 30-day and 90-day mortality in patients with cerebral infarction admitted to the intensive care unit (ICU).

In this retrospective observational study, 1,089 patients with cerebral infarction were recruited. The concentration of blood lactate and serum albumin on the first day of ICU admission were recorded. The relationship between LAR levels and mortality was evaluated through univariate and multivariate Cox regression analyses, four-knot multivariate restricted cubic spline regression, and Kaplan-Meier (KM) curves.

The overall 30-day and 90-day mortality rates in the entire cohort were 27.3 and 35.8%, respectively. KM analysis revealed a significant relationship between high LAR index and the risk of all-cause mortality (log-rank p < 0.001). Furthermore, multivariate Cox proportional risk analysis showed that the LAR index independently predicted the risk of 30-day mortality (HR: 1.38, 95% CI 1.15-1.64, p = 0.004) and 90-day mortality (HR: 1.53, 95% CI 1.32-1.77, p < 0.001) in the study population. Furthermore, a higher LAR exceeding 0.53 was positively correlated with the risk of 30-day and 90-day mortalities. Subsequent subgroup analyses demonstrated that LAR could predict the primary outcome.

In summary, the LAR index is a reliable and independent predictor of increased mortality among critically ill patients suffering from cerebral infarction. Nonetheless, there is a need for additional comprehensive prospective studies to validate these findings.

Alpha-fetoprotein (AFP), a serum glycoprotein, is expressed during embryonic development and the pathogenesis of liver cancer. It serves as a clinical tumor marker, function as a carcinogen, immune suppressor, and transport vehicle; but the detailed AFP structural information has not yet been reported. In this study, we used single-particle cryo-electron microscopy(cryo-EM) to analyze the structure of the recombinant AFP obtained a 3.31 Å cryo-EM structure and built an atomic model of AFP. We observed and identified certain structural features of AFP, including N-glycosylation at Asn251, four natural fatty acids bound to distinct domains, and the coordination of metal ions by residues His22, His264, His268, and Asp280. Furthermore, we compared the structural similarities and differences between AFP and human serum albumin. The elucidation of AFP's structural characteristics not only contributes to a deeper understanding of its functional mechanisms, but also provides a structural basis for developing AFP-based drug vehicles.

Albumin continues to be used routinely by cardiac anaesthesiologists perioperatively despite lack of evidence for improved outcomes. The Multicenter Perioperative Outcomes Group (MPOG) data ranked our institution as one of the highest intraoperative albumin users during cardiac surgery. Therefore, we designed a quality improvement project (QIP) to introduce a bundle of interventions to reduce intraoperative albumin use in cardiac surgical patients.

Our institutional MPOG data were used to analyse the FLUID-01-C measure that provides the number of adult cardiac surgery cases where albumin was administered intraoperatively by anaesthesiologists from 1 July 2019 to 30 June 2022. The QIP involved introduction of the following interventions: (1) education about appropriate albumin use and indications (January 2021), (2) email communications reinforced with OR teaching (March 2021), (3) removal of albumin from the standard pharmacy intraoperative medication trays (April 2021), (4) grand rounds presentation discussing the QIP and highlighting the interventions (May 2021) and (5) quarterly provider feedback (starting July 2021). Multivariable segmented regression models were used to assess the changes from preintervention to postintervention time period in albumin utilisation, and its total monthly cost.

Among the 5767 cardiac surgery cases that met inclusion criteria over the 3-year study period, 16% of patients received albumin intraoperatively. The total number of cases that passed the metric (albumin administration was avoided), gradually increased as our interventions went into effect. Intraoperative albumin utilisation (beta=-101.1, 95% CI -145 to -56.7) and total monthly cost of albumin (beta=-7678, 95% CI -10712 to -4640) demonstrated significant decrease after starting the interventions.

At a single academic cardiac surgery programme, implementation of a bundle of simple and low-cost interventions as part of a coordinated QIP were effective in significantly decreasing intraoperative use of albumin, which translated into considerable costs savings.

Bovine serum albumin (BSA) plays a crucial role in cell culture media, influencing cellular processes such as proliferation and differentiation. Although it is commonly included in chondrogenic differentiation media, its specific function remains unclear. This study explores the effect of different BSA concentrations on the chondrogenic differentiation of human adipose-derived stromal/stem cells (hASCs). hASC pellets from six donors were cultured under chondrogenic conditions with three BSA concentrations. Surprisingly, a lower BSA concentration led to enhanced chondrogenesis. The degree of this effect was donor-dependent, classifying them into two groups: (1) high responders, forming at least 35% larger, differentiated pellets with low BSA in comparison to high BSA; (2) low responders, which benefitted only slightly from low BSA doses with a decrease in pellet size and marginal differentiation, indicative of low intrinsic differentiation potential. In all cases, increased chondrogenesis was accompanied by hypertrophy under low BSA concentrations. To the best of our knowledge, this is the first study showing improved chondrogenicity and the tendency for hypertrophy with low BSA concentration compared to standard levels. Once the tendency for hypertrophy is understood, the determination of BSA concentration might be used to tune hASC chondrogenic or osteogenic differentiation.

Non-alcoholic fatty liver disease (NAFLD) is a high-prevalence and progressive disorder. Due to lack of reliable in vitro models to recapitulate the consecutive phases, the exact pathogenesis mechanism of this disease and approved therapeutic medications have not been revealed yet. It has been proven that the interplay between multiple hepatic cell types and liver extracellular matrix (ECM) are critical in NAFLD initiation and progression. Herein, a liver microtissue (LMT) consisting of Huh-7, THP-1, and LX-2 cell lines and human umbilical vein endothelial cells (HUVEC), which could be substituted for the main hepatic cells (hepatocyte, Kupffer, stellate, and sinusoidal endothelium, respectively), encapsulated in liver derived ECM-Alginate composite, was bioengineered. When the microtissues were treated with free fatty acids (FFAs) including Oleic acid (6.6×10-4M) and Palmitic acid (3.3×10-4M), they displayed the key features of NAFLD, including similar pattern of transcripts for genes involved in lipid metabolism, inflammation, insulin-resistance, and fibrosis, as well as pro-inflammatory and pro-fibrotic cytokines' secretions and intracellular lipid accumulation. Continuing FFAs supplementation, we demonstrated that the NAFLD phenomenon was established on day 3 and progressed to the initial fibrosis stage by day 8. Furthermore, this model was stable until day 12 post FFAs withdrawal on day 3. Moreover, administration of an anti-steatotic drug candidate, Liraglutide (15 μM), on the NAFLD microtissues significantly ameliorated the NAFLD phenomenon. Overall, we bioengineered a drug-responsive, cost-benefit liver microtissues which can simulate the initiation and progression of NAFLD. It is expected that this platform could potentially be used for studying molecular pathogenesis of NAFLD and high-throughput drug screening. See also the graphical abstract(Fig. 1).

No studies have investigated the association between albumin levels and the risk of early cardiovascular complications in patients with ischemic stroke.

Retrospective analysis with a federated research network (TriNetX) based on electronic medical records (International Classification of Diseases-Tenth Revision-Clinical Modification and logical observation identifiers names and codes) mainly reported between 2000 and 2023, from 80 health care organizations in the United States. Based on albumin levels measured at admission to the hospital, patients with ischemic stroke were categorized into 2 groups: (1) reduced (≤3.4 g/dL) and (2) normal (≥3.5 g/dL) albumin levels. The primary outcome was a composite of all-cause death, heart failure, atrial fibrillation, ventricular arrhythmias, myocardial infarction, and Takotsubo cardiomyopathy 30 days from the stroke. Secondary outcomes were the risk for each component of the primary outcome. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% CIs following propensity score matching.

Overall, 320 111 patients with stroke had normal albumin levels (70.9±14.7 years; 48.9% females) and 183 729 (57.4%) had reduced albumin levels (72.9±14.3 years; 50.3% females). After propensity score matching, the primary outcomes occurred in 36.0% of patients with reduced and 26.1% with normal albumin levels (HR, 1.48 [95% CI, 1.46-1.50]). The higher risk in patients with reduced albumin levels was consistent also for all-cause death (HR, 2.77 [95% CI, 2.70-2.84]), heart failure (HR, 1.31 [95% CI, 1.29-1.34]), atrial fibrillation (HR, 1.11 [95% CI, 1.09-1.13]), ventricular arrhythmias (HR, 1.38 [95% CI, 1.30-1.46]), myocardial infarction (HR, 1.60 [95% CI, 1.54-1.65]), and Takotsubo cardiomyopathy (HR, 1.51 [95% CI, 1.26-1.82]). The association between albumin levels and the risk of cardiovascular events was independent of advanced age, sex, multimorbidity, and other causes of hypoalbuminemia. A progressively increased risk of adverse events was found in patients with mild and severe reduced compared to normal albumin levels.

Albumin levels are associated with the risk of early cardiovascular events and death in patients with ischemic stroke. The potential pathophysiological or therapeutic roles of albumin in patients with stroke warrant further investigation.

This study examined the effectiveness of coating demineralized bone matrix (DBM) with amorphous calcium phosphate (DBM + CaP), as well as a composite of DBM, calcium phosphate, and serum albumin (DBM + CaP + BSA). The intact structure of DBM promotes the transformation of amorphous calcium phosphate (CaP) into dicalcium phosphate dihydrate (DCPD) with a characteristic plate shape and particle size of 5-35 µm. The inclusion of BSA in the coating resulted in a better and more uniform distribution of CaP on the surface of DBM trabeculae. MG63 cells showed that both the obtained forms of CaP and its complex with BSA did not exhibit cytotoxicity up to a concentration of 10 mg/mL in vitro. Ectopic (subcutaneous) implantation in rats revealed pronounced biocompatibility, as well as strong osteoconductive, osteoinductive, and osteogenic effects for both DBM + CaP and DBM + CaP + BSA, but more pronounced effects for DBM + CaP + BSA. In addition, for the DBM + CaP + BSA samples, there was a pronounced full physiological intrafibrillar biomineralization and proangiogenic effect with the formation of bone-morrow-like niches, accompanied by pronounced processes of intramedullary hematopoiesis, indicating a powerful osteogenic effect of this composite.

Human serum albumin (HSA) is a multi-domain macromolecule with diverse ligand binding capability because of its ability to allow allosteric modulation despite being a monomeric protein. Physiologically, HSA act as the primary carrier for various exogenous and endogenous compounds and fatty acids, and alter the pharmacokinetic properties of several drugs. It has antioxidant properties and is utilized therapeutically to improve the drug delivery of pharmacological agents for the treatment of several disorders. The flexibility of albumin in holding various types of drugs coupled with a variety of modifications makes this protein a versatile drug carrier with incalculable potential in therapeutics. This review provides a brief outline of the different structural properties of HSA, and its various binding sites, moreover, an overview of the genetic, biomedical, and allosteric modulation of drugs and drug delivery aspects of HSA is also included, which may be helpful in guiding advanced clinical applications and further research on the therapeutic potential of this extraordinary protein.

While the association between decreased serum albumin (ALB) levels and increased risk of acute kidney injury (AKI) is well established, the risk of death among patients with AKI with low serum ALB levels is unclear. We aimed to evaluate the association between serum ALB levels in patients with AKI and mortality, and help guide their clinical management.

The included patients were those diagnosed with AKI and admitted to Zhejiang Provincial People's Hospital between January 2018 and December 2020. The clinical endpoint was all-cause mortality rate at 90-days and 1-year. Patients were divided into four groups according to the quartiles (Qs) of ALB measurements at admission. Cumulative survival curves were calculated using Kaplan-Meier analysis, and Cox proportional risk models were used to assess the association between serum ALB levels and 90-day and 1-year all-cause mortality.

This study included 740 patients with AKI. Patients with measured ALB values were classified into quartiles: Q1 ≤ 26.0 g/L (n = 188); Q2 = 26.1-30.5 g/L (n = 186); Q3 = 30.6-34.7 g/L (n = 183); Q4 ≥ 34.8 g/L (n = 183). Univariate analysis using Cox regression showed that for every 10 g/L increase in ALB, the 90-day and 1-year mortality decreased by 29%. Among the four subgroups, patients with lower ALB levels had a higher risk of death. After adjusting for demographics, comorbid conditions, inflammatory index, and medicine, the lowest ALB quartile (ALB < 26 g/L) was associated with increased risk of 90-day mortality (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.30 to 2.38, P < 0.001) and 1-year all-cause mortality (HR, 1.79; 95% CI, 1.33 to 2.41, P < 0.001).

ALB levels in patients with AKI were significantly correlated with prognosis, and the higher the level, the better the prognosis. Compared to patients with ALB ≥ 34.8 g/L, patients with 26.1 g/L < ALB ≤ 30.5 g/L had an increased risk of 90-day and 1-year all-cause mortality of approximately 40%, and patients with ALB ≤ 26.0 g/L had an increased risk of 90-day and 1-year all-cause mortality of approximately 76% and 79%, respectively.

Hybrid nanoflowers are structures consisting of organic (enzymes, proteins, nucleic acids) and inorganic components (mostly metal phosphates) with a flower-like hierarchical structure. Novel hybrid nanoflowers based on bovine serum albumin (BSA) and hydroxyapatite (HA) were obtained and characterized. Study on BSA-HA nanoflowers as potential drug delivery system is reported for the first time.

Embedding ciprofloxacin in the structure of hybrid nanoflowers was confirmed by ATR-FTIR and thermogravimetric analysis. The inorganic phase of the nanoflowers was determined by X-ray diffraction. UV‒Vis spectroscopy was used to evaluate the release profiles of ciprofloxacin from nanoflowers in buffer solutions at pH 7.4 and 5. The agar disk diffusion method was used to study the antibacterial activity of the synthesized nanoflowers against Staphylococcus aureus and Pseudomonas aeruginosa.

Bovine serum albumin - hydroxyapatite nanoflowers were obtained with diameters of ca. 1-2 µm. The kinetics of ciprofloxacin release from nanoflowers were described by the Korsmeyer-Peppas model. The antibacterial activity of the synthesized nanoflowers was demonstrated against S. aureus and P. aeruginosa, two main pathogens found in osteomyelitis.

The formulated nanoflowers may act as an efficient local antibiotic delivery system. Due to the use of nonhazardous, biodegradable components and benign synthesis, hybrid nanoflowers are very promising drug delivery systems that could be applied in the treatment of skeletal system infections.

Hepatocellular carcinoma (HCC) is a significant global health burden, with postoperative hospital length of stay (LOS) impacting patient outcomes and healthcare costs. Existing nutritional, inflammatory, and coagulation indices can predict LOS, with particular interest in albumin, fibrinogen, and D-dimer. This study investigates the predictive value of preoperative albumin-to-fibrinogen ratio (AFR) and albumin-to-D-dimer ratio (ADR) for postoperative LOS in HCC patients.

This retrospective study involved 462 adult HCC patients who underwent partial hepatic lesion excision between February 2016 and August 2022. We analyzed demographic and clinical data, including preoperative blood samples, surgical approach, and LOS. The primary outcome measure was LOS, calculated from the date of surgery to the date of hospital discharge. Preoperative AFR and ADR were calculated. The ROC curves determined optimal cutoff points. The Cox proportional hazards model, Kaplan-Meier method, and the log-rank test were used for statistical analysis.

The study established an optimal AFR cutoff value of 15.474, with a higher AUC value than ADR, indicating superior predictive potential for postoperative LOS. Participants with high-AFR (AFR > 15.474) had a shorter median LOS (13 vs. 15 days, p < 0.001) compared to those with low-AFR (AFR ≤15.474). Multivariate analysis revealed high-AFR (HR: 1.99; p < 0.001) as a positive influence on LOS reduction, whereas Child-Pugh rated as B (HR: 0.49; p < 0.001), laparotomy (HR: 0.37; p < 0.001) and total bilirubin >20.5 μmol/L (HR: 0.58; p < 0.001) negatively impacted LOS reduction. Subgroup analysis confirmed AFR's predictive ability for patients experiencing reduced or prolonged LOS due to Child-Pugh score, surgical methods, and total bilirubin concentrations. Even within normal albumin and fibrinogen levels, patients with high-AFR exhibited a shorter LOS (all p < 0.001).

Our findings underscore the value of the AFR as a reliable predictor of LOS in HCC patients. An AFR greater than 15.474 consistently correlated with a shorter LOS, suggesting its potential clinical utility in guiding perioperative management and resource allocation in HCC patients.

The relationship between non-communicable diseases and eating behaviour has long been attributed to a surplus of food and energy. However, the increase in the prevalence of non-communicable disease and their underlying low-grade inflammatory milieu among people of low socio-economic status has highlighted the existence of a confounding factor. In this work, we aim to study the effect of lysine deficiency on some inflammatory markers in the absence or presence of an inflammatory insult (lipopolysaccharide (LPS)). For this purpose, thirty-two 5-week-old male Sprague Dawley rats were randomly distributed into four groups: (1) control diet, (2) control diet+LPS, (3) lysine-deficient diet and (4) lysine-deficient diet + LPS. Groups were only allowed their experimental diets for 4 weeks, during which LPS (50 µg/kg) or saline injections were administered intraperitoneally three times per week. The study showed that lysine deficiency blunted growth and body compartments development, decreased albumin production and elevated liver C-reactive protein (CRP) expression, independently of IL-6 and IL-1β, the main precursors of CRP. Also, the insufficient levels of lysine in the diet increased hyperactivity and triggered an anxiety-like behaviour, exacerbated with LPS. This work presents evidence that various physiological changes are associated with the absence of a sufficient amount of lysine in the diet and can potentially increase the risk factor for diseases. Thus, the increment in non-communicable disease among the low socio-economic status populations, who heavily rely on cereals as a main source of protein, can be, at least partially, blamed on low lysine availability in diets.

Previous studies have indicated that some blood metrics play a crucial role in the diagnostic and prognostic values of various solid tumours. However, their comprehensive and unbiased comparison for nasopharyngeal carcinoma (NPC) has not been performed. Twenty blood metrics evaluated in tumours or noncancerous diseases were selected. We selected 1089 patients with NPC and analyzed the relationship between these metrics, clinical characteristics, and overall survival (OS). The albumin and prognostic nutritional index (PNI) exhibited a high area under the curve (AUC) value (> 0.7) together with high "sensitivity (Sen) + specificity (Spe) (> 1.5)" or Youden index (> 0.5) when compared to healthy populations. In comparing NPC and nasal polyps, 9 of 20 blood metrics showed a high AUC value (> 0.7). However, only the PNI and international normalised ratio show a sufficiently high Sen + Spe or Youden Index. None of them could distinguish the status of the TNM classification well. Only the lymphocyte-to-monocyte ratio (LMR) could predict the OS of patients with NPC (cut-off, 4.91; p = 0.0069). Blood metrics as non-invasive biomarkers are valuable tools for clinical management. Among these indicators, PNI is the most ideal indicator to distinguish NPC from healthy and nasal polyps. The LMR has good prognostic value.

Human serum albumin (HSA) as the most abundant plasma protein carries multifunctional properties. A major determinant of the efficacy of albumin relies on its potent binding capacity for toxins and pharmaceutical agents. Albumin binding is impaired in pathological conditions, affecting its function as a molecular scavenger. Limited knowledge is available on the functional properties of albumin in critically ill patients with sepsis or septic shock. A prospective, non-interventional clinical trial assessed blood samples from 26 intensive care patients. Albumin-binding capacity (ABiC) was determined by quantifying the unbound fraction of the fluorescent marker, dansyl sarcosine. Electron paramagnetic resonance fatty acid spin-probe evaluated albumin's binding and detoxification efficiencies. Binding efficiency (BE) reflects the strength and amount of bound fatty acids, and detoxification efficiency (DTE) indicates the molecular flexibility of patient albumin. ABiC, BE, and DTE effectively differentiated control patients from those with sepsis or septic shock (AUROC > 0.8). The diagnostic performance of BE showed similarities to procalcitonin. Albumin functionality correlates with parameters for inflammation, hepatic, or renal insufficiency. Albumin-binding function was significantly reduced in critically ill patients with sepsis or septic shock. These findings may help develop patient-specific algorithms for new diagnostic and therapeutic approaches.

Twenty per cent albumin (1.5 g/kg at diagnosis and 1 g/kg on day three, infused over six-hour duration) is recommended particularly in high-risk spontaneous bacterial peritonitis (SBP). Whether reduced dose albumin infusion is as effective as the standard dose albumin infusion is not clear. The aim of this study was to compare standard dose albumin infusion with reduced dose albumin infusion in acute kidney injury (AKI) development or progression in patients with cirrhosis and high-risk SBP.

Sixty-three patients were randomized to the standard dose albumin arm (n = 31) and reduced dose albumin arm (n = 32, 0.75 g/kg at diagnosis and 0.5 g/kg 48 h later). The albumin was infused over six-hour duration in both groups. When the patient developed respiratory distress, the albumin infusion was stopped and that dose (i.e. of day one or day three) was not restarted and no attempt was made to finish the whole dose of that day. However, the next dose was started at the pre-calculated infusion rate if there was no evidence of respiratory distress at the start of next infusion.

All 31 patients in standard dose and two (6.25%) in the reduced dose group developed symptomatic circulatory overload (p < 0.001), with infusions being stopped prematurely. The actual albumin dose received on day one was similar in both groups and only slightly higher in the standard dose group on day three. Resolution of SBP, progression of AKI to higher stage, in-hospital mortality and 28 days' mortality were similar in both groups.

For treatment of SBP, standard dose albumin infusion (1.5 g/kg at diagnosis and 1 g/kg 48 hours later) infused over six hours is not tolerated by Indian patients. The effectiveness of standard dose albumin infused over more prolonged periods, as compared to reduced dose albumin, should be evaluated in further studies.

Clinical Trials.gov Identifier: NCT04273373 .

Activated stellate cells play a role in fibrosis development in the liver, pancreas, and kidneys. The fusion protein R-III, which consists of retinol-binding protein and albumin domain III, has been demonstrated to attenuate liver and renal fibrosis by suppressing stellate cell activation. In this study, we investigated the efficacy of R-III against bleomycin-induced lung fibrosis in mice. R-III reduced lung fibrosis and primarily localized in autofluorescent cells in the lung tissue. Furthermore, we isolated lung stellate cells (LSCs) from rat lungs using the isolation protocol employed for hepatic stellate cells (HSCs). LSCs shared many characteristics with HSCs, including the presence of vitamin A-containing lipid droplets and the expression of alpha-smooth muscle actin and collagen type I, markers for activated HSCs/myofibroblasts. LSCs spontaneously transdifferentiated into myofibroblasts in in vitro culture, which was inhibited by R-III. These findings suggest that R-III may reduce lung fibrosis by inactivating LSCs and could be a promising treatment for extrahepatic fibrosis.

Humans respond profoundly to changes in diet, while nutrition and environment have a great impact on population health. It is therefore important to deeply characterize the human nutritional responses.

Endocrine parameters and the metabolome of human plasma are rapidly responding to acute nutritional interventions such as caloric restriction or a glucose challenge. It is less well understood whether the plasma proteome would be equally dynamic, and whether it could be a source of corresponding biomarkers.

We used high-throughput mass spectrometry to determine changes in the plasma proteome of i) 10 healthy, young, male individuals in response to 2 days of acute caloric restriction followed by refeeding; ii) 200 individuals of the Ely epidemiological study before and after a glucose tolerance test at 4 time points (0, 30, 60, 120 minutes); and iii) 200 random individuals from the Generation Scotland study. We compared the proteomic changes detected with metabolome data and endocrine parameters.

Both caloric restriction and the glucose challenge substantially impacted the plasma proteome. Proteins responded across individuals or in an individual-specific manner. We identified nutrient-responsive plasma proteins that correlate with changes in the metabolome, as well as with endocrine parameters. In particular, our study highlights the role of apolipoprotein C1 (APOC1), a small, understudied apolipoprotein that was affected by caloric restriction and dominated the response to glucose consumption and differed in abundance between individuals with and without type 2 diabetes.

Our study identifies APOC1 as a dominant nutritional responder in humans and highlights the interdependency of acute nutritional response proteins and the endocrine system.

Medulloblastoma is a tumor of the cerebellum that metastasizes to the leptomeninges of the central nervous system (CNS), including to forebrain and to spinal cord. The inhibitory effect of polynitroxylated albumin (PNA), a caged nitroxide nanoparticle, on leptomeningeal dissemination and metastatic tumor growth was studied in a Sonic Hedgehog transgenic mouse model. PNA treated mice showed an increased lifespan with a mean survival of 95 days (n = 6, P<0.05) compared with 71 days in controls. In primary tumors, proliferation was significantly reduced and differentiation was significantly increased (P<0.001) as shown by Ki-67+ and NeuN+ immunohistochemistry, while cells in spinal cord tumors appeared unaffected. Yet, histochemical analysis of metastatic tumor in spinal cord showed that the mean total number of cells in spinal cord was significantly reduced in mice treated with PNA compared to albumin vehicle (P<0.05). Examination of various levels of the spinal cord showed that PNA treated mice had significantly reduced metastatic cell density in the thoracic, lumbar and sacral spinal cord levels (P<0.05), while cell density in the cervical region was not significantly changed. The mechanism by which PNA may exert these effects on CNS tumors is discussed.

As one of the most popular sources for fish albumin, Channa striata has been considered as a promising substitute for human albumin. However, scientific information regarding its genomic and proteomic is very limited, making its identification rather complicated. In this study, we aimed to isolate, characterize, and examine the bioactivity of protein and peptide derivatives of C. striata albumin. Fractionation of albumin from C. striata extract was conducted using Cohn Process and the yield was evaluated. The peptides were further produced by enzymatic hydrolysis. All these proteins were studied using tricine-SDS PAGE and tested for in vitro ACE inhibition. Dry weights of the Fraction-5, where the albumin was more abundant and purer, was 3.8 ± 2.1%. Based on tricine-SDS PAGE analysis, two bands of protein, e.g., approximately 10 and 13 kDa, were detected with highest intensity found in Fraction-5, which might be albumin of C. striata. An increasing trend of ACE inhibition by the fractions was observed, ranging from 7.09 to 22.99%. The highest ACEI activity was found in peptides from alcalase hydrolysis with molecular size <3 kDa (56.65 ± 2.32%, IC₅₀ 36.93 μg/mL). This value was also statistically significant compared with the non-hydrolyzed Fraction-5 and Parental Fraction, which were 23.48 ± 3.11% (P < 0.05) and 13.02 ± 0.68% (P < 0.01), respectively. Taken together, these findings suggest a promising potential of peptide-derived C. striata albumin for natural antihypertensive agents.

The food sector uses methyl yellow (MY) extensively as a colorant. The primary transporter in vivo that influences MY absorption, metabolism, distribution, and excretion is human serum albumin (HSA). Exploring the binding process and looking at how HSA and MY work physiologically at the molecular level is therefore very important. Experiments using steady-state fluorescence and fluorescence lifetimes proved that HSA and MY's quenching mechanisms were static. The HSA-MY complex's binding constant was estimated using thermodynamic parameters to be around 10⁴ M^-1. The hydrophobic forces were a major factor in the binding process, as evidenced by the negative ΔG, positive ΔH, and ΔS, which suggested that this contact was spontaneous. Site tests showed that MY linked to HSA's site I. Circular dichroism and three-dimensional fluorescence analysis revealed that the 1.33% α-helix content dropped and the amino acid microenvironment altered. While HSA's protein surface hydrophobicity decreased when engaging MY, the binding of MY to HSA reduced in the presence of urea. The stability of the system was assessed using molecular modeling. Additionally, HSA's esterase-like activity decreased when MY was present, and Ibf/Phz affected the inhibition mechanism of MY on HSA. These findings offer a distinctive perspective for comprehending the structure and functioning of HSA and evaluating the safety of MY.

Significance: Increased plasma concentrations of total homocysteine (tHcy; mild-moderate hyperhomocysteinemia: 15-50 μM tHcy) are considered an independent risk factor for the onset/progression of various diseases, but it is not known about how the increase in tHcy causes pathological conditions. Recent Advances: Reduced homocysteine (HSH ∼1% of tHcy) is presumed to be toxic, unlike homocystine (∼9%) and mixed disulfide between homocysteine and albumin (HSS-ALB; homocysteine [Hcy]-albumin mixed disulfide, ∼90%). This and other notions make it difficult to explain the pathogenicity of Hcy because: (i) lowering tHcy does not improve pathological outcomes; (ii) damage due to HSH usually emerges at supraphysiological doses; and (iii) it is not known why tiny increments in plasma concentrations of HSH can be pathological. Critical Issues: Albumin may have a role in Hcy toxicity, because HSS-ALB could release toxic HSH via thiol-disulfide (SH/SS) exchange reactions in cells. Similarly, thiol-disulfide exchange processes of reduced albumin (albumin with free SH group of Cys34 [HS-ALB]) or N-homocysteinylated albumin are plausible alternatives for initiating Hcy pathological events. Adverse effects of albumin and other data reviewed here suggest the hypothesis of a role of albumin in Hcy toxicity. Future Directions: HSS-ALB might be involved in disruption of the antioxidant/oxidant balance in critical tissues (brain, liver, kidney). Since homocysteine-albumin mixed disulfide is a possible intermediate of thiol-disulfide exchange reactions, we suggest that homocysteinylated albumin could be a new pathological factor, and that studies on the redox role of albumin and mixed disulfide production via thiol-disulfide exchange reactions could offer new therapeutic insights for reducing Hcy toxicity.