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Showing papers on "Serum albumin published in 2016"


Journal ArticleDOI
TL;DR: Clinically, reduced CP appears to be a result rather than a cause of ill-health, and therapy designed to increase CP has limited benefit, while the ubiquitous occurrence of hypoalbuminemia in disease states limits the diagnostic utility of the CP measurement.
Abstract: Serum albumin concentration (CP) is a remarkably strong prognostic indicator of morbidity and mortality in both sick and seemingly healthy subjects. Surprisingly, the specifics of the pathophysiology underlying the relationship between CP and ill-health are poorly understood. This review provides a summary that is not previously available in the literature, concerning how synthesis, catabolism, and renal and gastrointestinal clearance of albumin interact to bring about albumin homeostasis, with a focus on the clinical factors that influence this homeostasis. In normal humans, the albumin turnover time of about 25 days reflects a liver albumin synthesis rate of about 10.5 g/day balanced by renal (≈6%), gastrointestinal (≈10%), and catabolic (≈84%) clearances. The acute development of hypoalbuminemia with sepsis or trauma results from increased albumin capillary permeability leading to redistribution of albumin from the vascular to interstitial space. The best understood mechanism of chronic hypoalbuminemia is the decreased albumin synthesis observed in liver disease. Decreased albumin production also accounts for hypoalbuminemia observed with a low-protein and normal caloric diet. However, a calorie- and protein-deficient diet does not reduce albumin synthesis and is not associated with hypoalbuminemia, and CP is not a useful marker of malnutrition. In most disease states other than liver disease, albumin synthesis is normal or increased, and hypoalbuminemia reflects an enhanced rate of albumin turnover resulting either from an increased rate of catabolism (a poorly understood phenomenon) or enhanced loss of albumin into the urine (nephrosis) or intestine (protein-losing enteropathy). The latter may occur with subtle intestinal pathology and hence may be more prevalent than commonly appreciated. Clinically, reduced CP appears to be a result rather than a cause of ill-health, and therapy designed to increase CP has limited benefit. The ubiquitous occurrence of hypoalbuminemia in disease states limits the diagnostic utility of the CP measurement.

399 citations


Journal ArticleDOI
TL;DR: This review article summarizes the mainstream chemical strategies of developing HSA binding molecules for coupling with drug molecules, and concisely condense the recent progress of the most important clinical applications of HSA-binding platforms.
Abstract: Albumin is the most abundant circulating protein in plasma and has recently emerged as a versatile protein carrier for drug targeting and for improving the pharmacokinetic profile of peptide or protein based drugs. Three drug delivery technologies related to albumin have been developed, which include the coupling of low-molecular weight drugs to exogenous or endogenous albumin, conjugating bioactive proteins by albumin fusion technology (AFT), and encapsulation of drugs into albumin nanoparticles. This review article starts with a brief introduction of human serum albumin (HSA), and then summarizes the mainstream chemical strategies of developing HSA binding molecules for coupling with drug molecules. Moreover, we also concisely condense the recent progress of the most important clinical applications of HSA-binding platforms, and specify the current challenges that need to be met for a bright future of HSA-binding.

293 citations


Journal ArticleDOI
TL;DR: Elevated plasma levels of fibrinogen and TNF-α and decreased serum albumin are associated with rapid loss of kidney function in patients with CKD.
Abstract: Background and objectives CKD is a global public health problem with significant mortality and morbidity. Design, setting, participants, & measurements We examined the multivariable association of plasma levels of IL-1, IL-1 receptor antagonist, IL-6, TNF- α , TGF- β , high–sensitivity C–reactive protein, fibrinogen, and serum albumin with progression of CKD in 3430 Chronic Renal Insufficiency Cohort study participants. Results Over a median follow-up time of 6.3 years, 899 participants reached the composite end point of ≥50% decline in eGFR from baseline or onset of ESRD. Elevated plasma levels of fibrinogen, IL-6, and TNF- α and lower serum albumin were associated with a greater decline in eGFR over time. After adjusting for demographics, BP, laboratory variables, medication use, and baseline eGFR, hazard ratios for the composite outcome were greater for the patients in the highest quartile of fibrinogen (hazard ratio, 2.05; 95% confidence interval, 1.64 to 2.55; P P α (hazard ratio, 1.94; 95% confidence interval, 1.52 to 2.47; P P P 0.001), serum albumin (hazard ratio, 1.52; 95% confidence interval, 1.24 to 1.87; P α (hazard ratio, 1.42; 95% confidence interval, 1.11 to 1.81; P Conclusions Elevated plasma levels of fibrinogen and TNF- α and decreased serum albumin are associated with rapid loss of kidney function in patients with CKD.

267 citations


Journal ArticleDOI
TL;DR: The particular advantages of albumin used in DDSs include ready availability, ease of chemical modification, good biocompatibility, and low immunogenicity.
Abstract: One of the biggest impacts that the nanotechnology has made on medicine and biology, has been in the area of drug delivery systems (DDSs). Many drugs suffer from serious problems concerning insolubility, instability in biological environments, poor uptake into cells and tissues, sub-optimal selectivity for targets and unwanted side effects. Nanocarriers can be designed as DDSs to overcome many of these drawbacks. One of the most versatile building blocks to prepare these nanocarriers is the ubiquitous, readily available and inexpensive protein, serum albumin. Areas covered: This review covers the use of different types of albumin (human, bovine, rat, and chicken egg) to prepare nanoparticle and microparticle-based structures to bind drugs. Various methods have been used to modify the albumin structure. A range of targeting ligands can be attached to the albumin that can be recognized by specific cell receptors that are expressed on target cells or tissues. Expert opinion: The particular advantages of albumin used in DDSs include ready availability, ease of chemical modification, good biocompatibility, and low immunogenicity. The regulatory approvals that have been received for several albumin-based therapeutic agents suggest that this approach will continue to be successfully explored.

222 citations


Journal ArticleDOI
TL;DR: This review highlights the various potential albumin–NP hybrids as nano drug carriers and the binding of albumin with NP is associated with conformational and functional modulations in protein as observed with silver, gold and superparamagnetic iron oxide NPs.
Abstract: Nanomaterials have been used widely for delivery of therapeutic agents. Protein-nanoparticle (NP) complexes have gained importance as vehicles for targeted drug delivery due to increased ease of administration, stability and half-life of drug, and reduced toxic side effects. Designing of phospholipid-bovine serum albumin (BSA) complexes and stealth NPs with BSA has paved the way for drug delivery carriers with prolonged blood circulation times. Preformed albumin corona has shown to decrease non-specific association and thereby reduce the clearance rate. Albumin corona has enabled the localization of drug carriers in specific tissues such as liver and heart, thus regulating biodistribution. Tailored albumin-NP conjugates have also enabled controlled degradation of NP and drug release. However, the binding of albumin with NP is associated with conformational and functional modulations in protein as observed with silver, gold and superparamagnetic iron oxide NPs. In this review, we highlight the various potential albumin-NP hybrids as nano drug carriers.

141 citations


Journal ArticleDOI
TL;DR: A TICT based NIR-fluorescent probe 3 has been designed and synthesized, which selectively detects HSA with fluorescence enhancement in blood plasma with a detection limit of 11 nM among the various proteins, nucleotides and thiols tested.

140 citations


Journal ArticleDOI
TL;DR: Administration of 20% exogenous albumin immediately before surgery increases urine output during surgery and reduces the risk of AKI after off-pump coronary artery bypass surgery in patients with a preoperative serum albumin level of less than 4.0 g/dl.
Abstract: Background:Hypoalbuminemia may increase the risk of acute kidney injury (AKI). The authors investigated whether the immediate preoperative administration of 20% albumin solution affects the incidence of AKI after off-pump coronary artery bypass surgery.Methods:In this prospective, single-center, ran

115 citations


Journal ArticleDOI
TL;DR: Reference intervals for serum albumin should be stratified by age and sex and until there is greater methodological standardization, laboratories should determine their own reference intervals and not accept a single consensus reference interval.
Abstract: BackgroundIn the UK, a common reference interval for serum albumin is widely used irrespective of age or sex. Implicit in this is that laboratories produce analytically similar results. This paper ...

112 citations


Journal ArticleDOI
TL;DR: It is proven that C-dots showed little influence on the conformation of HSA and γ-globulins, and the interaction between C- dots and two kinds of serum proteins was driven by hydrophobic and van der waals forces.

107 citations


Journal ArticleDOI
TL;DR: Results demonstrate that fluorescence intensity of human serum albumin (HSA) gets quenched by NIB and quenching occurs in static manner and nintedanib increase the thermostability of HSA.
Abstract: In this study, we have investigated the binding affinity of the newly approved tyrosine kinase inhibitor nintedanib (NIB) with human serum albumin under simulated physiological condition. The obtained results demonstrate that fluorescence intensity of human serum albumin (HSA) gets quenched by NIB and quenching occurs in static manner. Binding parameters calculated from modified Stern-Volmer equation shows that the drug binds to human serum albumin with a binding constant in the order of 10(3), with the number of binding sites approximately equal to one. Synchronous fluorescence data deciphered the change in the microenvironment of tryptophan (Trp) residue in HSA. Circular dichroism data showed an increase in helical content upon drug binding. Dynamic light scattering measurements deciphered the reduction in hydrodynamic radii of the protein, further differential scanning calorimetry results shows that nintedanib increase the thermostability of HSA. Molecular docking results demonstrated that major binding forces involved in the complex formation are hydrogen bonding and hydrophobic interaction.

89 citations


Journal ArticleDOI
TL;DR: This study investigated the prognostic value of preoperative serum albumin in surgical patients with head and neck cancer (HNC) and found it to be positive.
Abstract: Objectives/Hypothesis Albumin is an indicator of nutritional status and has been investigated as a predictor of cancer survival and perioperative outcomes. This study investigated the prognostic value of preoperative serum albumin in surgical patients with head and neck cancer (HNC). Study Design Retrospective cohort study. Methods A chart review was performed of patients who underwent HNC resection over a 6-year period at a single institution. Statistical analyses including Cox proportional hazards models, Pearson's correlation, and logistic regression were used to identify relationships between preoperative serum albumin and postoperative outcomes. Albumin was analyzed as a continuous variable. Results A total of 604 patients were studied representing all cancer types. There was no association between albumin and pneumonia, flap complications, or length of stay. Albumin was found to have statistically significant inverse associations with overall survival (OS) (hazard ratio [HR] = 0.685, P < .001) and postoperative wound infection (HR = 0.455, P = .001). In multivariate analysis of OS, albumin did not achieve significance as an independent predictor (HR = 0.78, P = .064), whereas hemoglobin, age, and cancer stage remained significant. In a subgroup of 280 patients with upper aerodigestive squamous cell carcinoma (SCCA), albumin maintained significance in multivariate analysis of OS (HR = 0.74, P = .046). When controlling for preoperative radiotherapy, salvage surgery, and cancer stage in multivariate analysis, albumin was a significant predictor of wound infection (OR = 0.55, P = .018). Conclusions In patients with HNC, lower preoperative serum albumin is associated with an increased rate of wound infection and poorer OS. The effect on OS is most pronounced in patients with upper aerodigestive SCCA. Level of Evidence 2b Laryngoscope, 2016

Journal ArticleDOI
TL;DR: A novel methodology that combines the use of this high density photo-cross-linking data with conformational space search to investigate the structure of human serum albumin domains, from purified samples, and in its native environment, human blood serum is presented.

Journal ArticleDOI
TL;DR: An overview of serum albumin and different purification methods is summarized, which shows how many efforts have been accomplished to achieve albumin during a long period of time.
Abstract: As the most frequent plasma protein, albumin constitutes more than 50% of the serum proteins in healthy individuals. It has a key role in oncotic pressure maintenance and it is known as a versatile protein carrier for transportation of various endogenous and exogenous ligands. Reduced amounts of albumin in the body will lead to different kinds of diseases such as hypovolemia and hypoproteinemia. It also has various indications in shocks, burns, cardiopulmonary bypass, acute liver failure and etc. Further applications in research consist of cell culture supplement, drug delivery carrier and protein/drug stabilizer. So, the demand for albumin increased annually worldwide. Due to different applications of albumin, many efforts have been accomplished to achieve albumin during a long period of time. In this review, an overview of serum albumin and different purification methods are summarized.

Journal ArticleDOI
TL;DR: The ruthenium complex sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP-1339/IT139) has entered clinical trials as the more soluble alternative to the indazolium compound KP1019 and was administered intravenously in non-tumor bearing nude BALB/c mice and the Ru content was determined.

Journal ArticleDOI
TL;DR: ALB level and CRP/ALB ratio were useful biomarkers for identifying CD activity, especially in males, and it is suggested that, in addition to inflammation, assessment of patient nutritional status could also aid in identifyingCD activity.
Abstract: BACKGROUND Serum albumin (ALB) may be low during acute inflammation, but it is also affected by nutritional status. Therefore, we hypothesized that ALB and the C-reactive protein/ALB ratio (CRP/ALB) may be associated with disease activity in patients with Crohn's disease (CD). MATERIAL AND METHODS Altogether, 100 patients with CD and 100 age- and sex-matched healthy volunteers were retrospectively enrolled in the current study. The patients with CD were subdivided into patients with active disease (Crohn's Disease Activity Index >150) and those in remission. ALB levels, CRP levels, and lipid profiles were measured. RESULTS ALB and CRP levels and the CRP/ALB ratio were the most useful for differentiating between active and nonactive CD. ALB levels (r=-0.50, P 0.05). The AUCs corresponding to ALB level, CRP level, and CRP/ALB ratio were more prominent in males versus females (P<0.05). CRP level (14.55 mg/L), ALB level (34.35 g/L), and CRP/ALB ratio (0.69) had sensitivities of 67.7%, 72.6%, and 59.7%, and specificities of 73.7%, 78.9%, and 81.6%, respectively, for CD activity. CONCLUSIONS In the present retrospective study, we found that ALB level and CRP/ALB ratio were useful biomarkers for identifying CD activity, especially in males. These results suggest that, in addition to inflammation, assessment of patient nutritional status could also aid in identifying CD activity.

Journal ArticleDOI
TL;DR: An untargeted analytical scheme and bioinformatics pipeline for detecting, quantitating, and annotating Cys34 adducts in tryptic digests of human serum/plasma is developed and adduct features were both positively and negatively associated with smoking.
Abstract: An important but understudied class of human exposures is comprised of reactive electrophiles that cannot be measured in vivo because they are short-lived. An avenue for assessing these meaningful exposures focuses on adducts from reactions with nucleophilic loci of blood proteins, particularly Cys34 of human serum albumin, which is the dominant scavenger of reactive electrophiles in serum. We developed an untargeted analytical scheme and bioinformatics pipeline for detecting, quantitating, and annotating Cys34 adducts in tryptic digests of human serum/plasma. The pipeline interrogates tandem mass spectra to find signatures of the Cys34-containing peptide, obtains accurate masses of putative adducts, quantitates adduct levels relative to a “housekeeping peptide”, and annotates modifications based on a combination of retention time, accurate mass, elemental composition, and database searches. We used the adductomics pipeline to characterize 43 adduct features in archived plasma from healthy human subjects ...

Journal ArticleDOI
TL;DR: High AGR is a strong independent predictor of long-term RFS and CSS in patients with BUC undergoing RC and among patients with normal albumin levels, patients with higher globulin, but lower AGR have worse survival.
Abstract: Objective To date, only a few studies have demonstrated the prognostic value of pretreatment serum albumin in bladder urothelial carcinoma (BUC). The aim of this study was to evaluate the association between the pretreatment albumin/globulin ratio (AGR) and the survival of patients with BUC treated with radical cystectomy (RC). Materials and methods Data from 296 patients with BUC who underwent RC between June 2000 and June 2013 were analyzed. The AGR was calculated as follows: albumin/(total protein−albumin). The AGR was divided into 2 groups for receiver operating characteristics curve analysis. Survival was estimated using Kaplan-Meier analysis and compared using the log rank test. Cox proportional hazards models were used for univariate and multivariate survival analyses. Results Patients in the high AGR group (AGR≥1.60) had a lower 5-year recurrence-free mortality rate compared with those in the low AGR group (AGR P P P = 0.006) and CSS (hazard rate = 0.280; 95% CI: 0.115–0.683; P = 0.005). Moreover, in the subset of 167 patients with normal serum albumin (albumin of≥40.0 g/l), serum AGR continues to be an independent predictor of RFS ( P = 0.012) and CSS ( P = 0.008). Conclusions High AGR is a strong independent predictor of long-term RFS and CSS in patients with BUC undergoing RC. Additionally, among patients with normal albumin (≥40 g/l) levels, patients with higher globulin, but lower AGR have worse survival. The pretreatment AGR is an easily accessible and cheap to use for predicting mortality in patients with BUC treated by RC.

Journal ArticleDOI
TL;DR: The results showed that the IPS-2 had superior hepatoprotective effects by increasing the serum enzyme activities and bilirubin levels, decreasing the serum albumin and triglyceride levels, improving the hepatic antioxidant status, and ameliorating the liver structure damage.

Journal ArticleDOI
Rui Li1, Hao Yang1, Dianlong Jia1, Qianxue Nie1, Huawei Cai1, Qing Fan1, Lin Wan1, Lin Li1, Xiaofeng Lu1 
TL;DR: It is demonstrated that ABD fused to the N-terminus endows hTRAIL with albumin binding ability; once it enters the vasculature, ABD mediates binding with endogenous albumin, thus prolonging the half-life and enhancing the antitumor effect of hT RAIL.

Journal ArticleDOI
TL;DR: A novel multicellular spheroid-based hepatic differentiation protocol starting from embryoid bodies of hiPSC-EBs for robust mass production of human hepatocyte-like cells (HLCs) using two novel inhibitors of the Wnt pathway is developed.
Abstract: Treatment of acute liver failure by cell transplantation is hindered by a shortage of human hepatocytes. Current protocols for hepatic differentiation of human induced pluripotent stem cells (hiPSCs) result in low yields, cellular heterogeneity, and limited scalability. In the present study, we have developed a novel multicellular spheroid-based hepatic differentiation protocol starting from embryoid bodies of hiPSCs (hiPSC-EBs) for robust mass production of human hepatocyte-like cells (HLCs) using two novel inhibitors of the Wnt pathway. The resultant hiPSC-EB-HLCs expressed liver-specific genes, secreted hepatic proteins such as Albumin, Alpha Fetoprotein, and Fibrinogen, metabolized ammonia, and displayed cytochrome P450 activities and functional activities typical of mature primary hepatocytes, such as LDL storage and uptake, ICG uptake and release, and glycogen storage. Cell transplantation of hiPSC-EB-HLC in a rat model of acute liver failure significantly prolonged the mean survival time and resolved the liver injury when compared to the no-transplantation control animals. The transplanted hiPSC-EB-HLCs secreted human albumin into the host plasma throughout the examination period (2 weeks). Transplantation successfully bridged the animals through the critical period for survival after acute liver failure, providing promising clues of integration and full in vivo functionality of these cells after treatment with WIF-1 and DKK-1.

Journal ArticleDOI
TL;DR: Genetically encoded indicators for Ca2+ and microneme secretion are developed to better define the signaling pathways that regulate these processes in Toxoplasma gondii and reveal that micRONeme secretion is centrally controlled by protein kinase G and that this pathway is further augmented by elevation of intracellular Ca2+.

Journal ArticleDOI
TL;DR: In this article, the role of proximal tubule reabsorption and filtration in albumin excretion was investigated in two distinct animal models, including acute exogenous albumin overload and transgenic expression of diphtheria toxin receptor.
Abstract: Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level.

Journal ArticleDOI
TL;DR: The first crystal structures of mammalian albumins in complex with zinc are presented, together with accompanying zinc binding data, which allow identification of key zinc transport sites on human and equine albumins.
Abstract: Zinc is an essential nutrient in the body; it is required for the catalytic activity of many hundreds of human enzymes and virtually all biological processes, therefore its homeostasis and trafficking is of crucial interest. Serum albumin is the major carrier of Zn2+ in the blood and is required for its systemic distribution. Here we present the first crystal structures of human serum albumin (HSA) and equine serum albumin (ESA) in complex with Zn2+. The structures allow unambiguous identification of the major zinc binding site on these two albumins, as well as several further, weaker zinc binding sites. The major site in both HSA and ESA has tetrahedral geometry and comprises three protein ligands from the sidechains of His67, His247 and Asp249 and a water molecule. Isothermal titration calorimetric studies of a HSA H67A mutant confirm this to be the highest affinity Zn2+ site. Furthermore, analysis of Zn2+ binding to HSA and ESA proved the presence of secondary sites with 20–50-fold weaker affinities, which may become of importance under particular physiological conditions. Both calorimetry and crystallography suggest that ESA possesses an additional site compared to HSA, involving Glu153, His157 and His288. The His157 residue is replaced by Phe in HSA, incapable of metal coordination. Collectively, these findings are critical to our understanding of the role serum albumin plays in circulatory Zn2+ handling and cellular delivery.

Journal ArticleDOI
TL;DR: It is shown that fibrinogen to albumin ratio (FAR) is significantly related to SS in predicting the severity of CAD in patients with STEMI.
Abstract: Objective Previous studies show that serum fibrinogen levels are established risk factors for coronary artery disease (CAD) and that serum albumin levels are of a higher specificity and sensitivity in ST-elevation myocardial infarction (STEMI). In this study, we sought to evaluate the association between fibrinogen to albumin ratio (FAR) and the extent and severity of CAD evaluated by TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries (SYNTAX) Score (SS) in patients with STEMI. Methods A total of 278 patients with STEMI were included in the study. FAR was calculated using specified variables. The extent and severity of CAD were evaluated using the SS. The patients were divided into low- (SS Results There were significant differences in the mean age (P = .016), admission serum albumin (P = .041), serum fibrinogen (P 87 FAR predicted SS (sensitivity, 70%; specificity, 70%), and an area under the curve of 0.758 serum fibrinogen and albumin level was an independent predictor for SS in patients with STEMI (b = 0.039; 95% confidence interval, 0.016-0.062; P = .001 and b = − 6.906; 95% confidence interval, − 12.284 to − 1.527; P = .013, respectively). Conclusion In the present study, we showed that FAR is significantly related to SS in predicting the severity of CAD in patients with STEMI.

Journal ArticleDOI
TL;DR: A novel pyrene-conjugated squaraine fluorescent probe SQ-P, which could self-assemble into nanoparticles in aqueous solution through multiple interactions, was designed to selectively detect serum albumin with a turn-on response in the near infrared (NIR) region.

Journal ArticleDOI
TL;DR: Six Fe(III) compounds derived from 2-hydroxy-1-naphthaldehyde thiosemicarbazone (7-12) are synthesized and revealed that Fe compound binds to the hydrophobic cavity in the HSA IIA subdomain, and compound 12 and HSA-12 complex inhibit the growth of the liver tumor and has stronger targeting ability and therapeutic efficacy than compound 12 alone.
Abstract: To improve the selectivity, delivery, and activity of ferric (Fe) anticancer agents, we design prodrugs based on N-donor residues of the human serum albumin (HSA) carrier IIA subdomain. We synthesized six Fe(III) compounds derived from 2-hydroxy-1-naphthaldehyde thiosemicarbazone (7–12). HSA complex structure revealed that Fe compound binds to the hydrophobic cavity in the HSA IIA subdomain. Lys199 and His242 of HSA replace the two Cl atoms of Fe compound, coordinating with Fe3+. In vivo data revealed that compound 12 and HSA-12 complex inhibit the growth of the liver tumor and that the HSA-12 complex has stronger targeting ability and therapeutic efficacy than compound 12 alone. In addition, our results have shown that compound 12 and HSA-12 complex induce Bel-7402 cell death possible by several mechanisms.

Journal ArticleDOI
TL;DR: The present experiment showed that the binding of Amlodipine and Aspirin to HSA induced a conformational change of HSA, and it was identified that the protein binding of the first drug could be affected by the second drug.
Abstract: Human serum albumin (HSA) is the most frequent protein in blood plasma Albumin transports various compounds, preserves osmotic pressure, and buffers pH A unique feature of albumin is its ability to bind drugs and other bioactive molecules However, it is important to consider binary and ternary systems of two pharmaceuticals to estimate the effect of the first drug on the second one and physicochemical properties Different techniques including time-resolved, second-derivative and anisotropy fluorescence spectroscopy, resonance light scattering (RLS), critical induced aggregation concentration (C CIAC), particle size, zeta potential and stability analysis were employed in this assessment to elucidate the binding behavior of Amlodipine and Aspirin to HSA Moreover, isothermal titration calorimetric techniques were performed and the QSAR properties were applied to analyze the hydration energy and log P Multiple sequence alignments were also used to predict the structure and biological characteristics of the HSA binding site Time-resolved fluorescence spectroscopy showed interaction of both drugs to HSA based on a static quenching mechanism Subsequently, second-derivative fluorescence spectroscopy presented different values of parameter H in binary and ternary systems, which were suggested that tryptophan was in a more polar environment in the ternary system than in a binary system Moreover, the polydispersity index and results from mean number measurements revealed that the presence of the second drug caused a decrease in the stability of systems and increased the heterogeneity of complex It is also, observed that the gradual addition of HSA has led to a marked increase in fluorescence anisotropy (r) of Amlodipine and Aspirin which can be suggested that the drugs were located in a restricted environment of the protein as confirmed by Red Edge Excitation Shift (REES) studies The isothermal titration calorimetric technique demonstrated that the interaction of the drugs with HSA was an enthalpically-driven process The present experiment showed that the binding of Amlodipine and Aspirin to HSA induced a conformational change of HSA It was also identified that the protein binding of the first drug could be affected by the second drug Such results can be of great use for understanding the pharmacokinetic and pharmacodynamic mechanisms of drugs

Journal ArticleDOI
Tao Zhu1, Jianjun Du1, Wenbing Cao1, Jiangli Fan1, Xiaojun Peng1 
TL;DR: These microenvironment-sensitive SA1–4 exhibited excellent fluorescent capabilities in the fast, convenient, selective, and sensitive recognition of HSA, especially in the quantitative albumin assay in human urine for assessment of kidney function and diagnosis of renal disease.
Abstract: A series of microenvironment-sensitive fluorescent dyes, SA1–4, have been presented, which can light up human serum albumin (HSA) in aqueous media and solid state with colorful emissions as well as dramatic fluorescence enhancements respectively, based on twisted intramolecular charge transfer and molecular rotor strategy. These microenvironment-sensitive SA1–4 exhibited excellent fluorescent capabilities in the fast, convenient, selective, and sensitive recognition of HSA, especially in the quantitative albumin assay in human urine for assessment of kidney function and diagnosis of renal disease. Moreover, SA1–4/HSA complexes could be applied in fluorescence imaging in living cells.

Journal ArticleDOI
TL;DR: The PEGylated albumin polyion complex micelle with lysozyme led to nanoparticles between 15 and 25 nm in size depending on the BSA to Lyz ratio, which has great potential as a drug delivery vehicle for a new generation of cancer pharmaceuticals.

Journal ArticleDOI
TL;DR: The data of the present study determines the detailed evaluation of BSA adsorption on TiO2 nanoparticle along with mechanism and Adsorption kinetics.
Abstract: The use of nanoparticles in food or pharma requires a molecular-level perceptive of how NPs interact with protein corona once exposed to a physiological environment. In this study, the conformational changes of bovine serum albumin (BSA) were investigated in detail when exposed to different concentration of titanium dioxide nanoparticle by various techniques. To analyze the effects of NPs on proteins, the interaction between bovine serum albumin and titanium dioxide nanoparticles at different concentrations were investigated. The interaction, BSA conformations, kinetics, and adsorption were analyzed by dynamic light scattering, Fourier transform infrared spectroscopy and fluorescence quenching. Dynamic light scattering analysis confirms the interaction with major changes in the size of the protein. Fluorescence quenching analysis confirms the side-on or end-on interaction of 1.1 molecules of serum albumin to titanium dioxide nanoparticles. Further, pseudo-second order kinetics was determined with equilibrium contact time of 20min. The spectroscopic analysis suggests that there is a conformational change both at secondary and tertiary structure levels. A distortion in both α-helix and β-sheets was observed by Fourier transform infrared (FTIR) spectroscopy. Fluorescence quenching analysis confirms the interaction of a molecule of bovine serum albumin to the single TiO2 nanoparticle. Further, pseudo-second order kinetics was determined with equilibrium contact time of 20min. The data of the present study determines the detailed evaluation of BSA adsorption on TiO2 nanoparticle along with mechanism and adsorption kinetics.