Association between serum albumin levels and disease severity in adult patients with dengue: A 7-year retrospective cohort study in China's Mainland

Objective:To identify the association between serum albumin levels and disease severity among adult patients with dengue in China's Mainland.Methods:This retrospective cohort study analyzed the data of adult patients(aged≥18 years)hospitalized with laboratory-confirmed dengue in a tertiary center for infectious diseases from 2013 to 2019 in China's Mainland.Serum albumin levels were estimated and compared between patients with severe dengue and non-severe dengue.Additionally,the association between serum albumin levels and severe dengue was evaluated using a generalized linear model[relative risks(RR)].Multivariate logistic regression analysis was performed to identify the potential predictors of severe dengue.Results:Overall,1568 patients were included in this study.Of these patients,34(2.17%)developed severe dengue.The median serum albumin levels were significantly lower in patients with severe dengue than that in those with non-severe dengue(33 g/L vs.37 g/L,P<0.001).After adjustment for age,sex,and comorbidities,hypoalbuminemia(RR 4.877,95%CI 2.193-11.461,P<0.001)was found to be a predictor of severe dengue.Serum albumin levels(OR 1.303,95%CI 1.161-1.462,P<0.001)and age(OR 1.038,95%CI 1.017-1.061,P<0.001)were significant risk factors for severe dengue.The area under the curve for serum albumin levels to distinguish severe dengue was 0.787.Conclusions:Lower serum albumin levels were significantly associated with disease severity in adult patients with dengue.Hypoalbuminemia on admission resulted in at least a four-fold increased risk of severe dengue.

Correlation of serum albumin level on postoperative day 2 with hospital length of stay in patients undergoing emergency surgery for perforated peptic ulcer

BACKGROUND Perforated peptic ulcer(PPU)is a common emergency surgical condition and a significant cause of morbidity and mortality worldwide.While advances in surgical techniques have improved outcomes for patients with PPU,many factors still affect postoperative hospital stay and overall prognosis.One potential factor is the serum albumin(SA)level,a widely utilized marker of nutritional status that has been associated with length of stay and complications in various surgical procedures.AIM To clarify the correlation of SA level on postoperative day 2 with hospital length of stay(HLOS)in patients undergoing emergency surgery for perforated peptic ulcer(PPU).METHODS We retrospectively collected and analyzed clinical baseline data,including blood routine and SA levels,of patients who underwent emergency PPU surgery and postoperative treatment at the Lingnan Hospital,the Third Affiliated Hospital of Sun Yat-sen University between December 2012 and September 2021.Patients were grouped according to HLOS with 7 d as the cut-off value,and relevant indicators were analyzed using SPSS 26.0.RESULTS Of the 37 patients undergoing emergency surgery for PPU referred to our department,33 had gastric and 4 had duodenal ulcer perforation.The median HLOS was 10 d.There were 8 patients in the≤7-d group(median HLOS:7 d)and 29 patients in the>7-d group(median HLOS:10 d).The≤7-d group had markedly higher SA on postoperative day 2 than the>7-d group(37.7 g/L vs 32.6g/L;P<0.05).The SA level on postoperative day 2 was a protective factor for patients with HLOS>7 d(Odds ratio=0.629,P=0.015).The cut-off of SA on postoperative day 2 was 30.6g/L,with an area under the curve of 0.86 and a negative predictive value of 100%for the prediction of HLOS≤7 d.CONCLUSION The SA level on postoperative day 2 was associated with the HLOS in patients undergoing emergency surgery for PPU.The pre-and post-operative albumin levels should be monitored,and infusion of human SA should be considered in a timely manner.

Study on the secondary structure and hydration effect of human serum albumin under acidic pH and ethanol perturbation with IR/NIR spectroscopy

Human serum albumin(HSA)is the most abundant protein in plasma and plays an essential physiological role in the human body.Ethanol precipitation is the most widely used way to obtain HSA,and pH and ethanol are crucial factors affecting the process.In this study,infrared(IR)spectroscopy and near-infrared(NIR)spectroscopy in combination with chemometrics were used to investigate the changes in the secondary structure and hydration of HSA at acidic pH(5.6-3.2)and isoelectric pH when ethanol concentration was varied from 0%to 40%as a perturbation.IR spectroscopy combined with the two-dimensional correlation spectroscopy(2DCOS)analysis for acid pH system proved that the secondary structure of HSA changed significantly when pH was around 4.5.What's more,the IR spectroscopy and 2DCOS analysis showed different secondary structure forms under different ethanol concentrations at the isoelectric pH.For the hydration effect analysis,NIR spectroscopy combined with the McCabe-Fisher method and aquaphotomics showed that the free hydrogen-bonded water fluctuates dynamically,with ethanol at 0-20%enhancing the hydrogen-bonded water clusters,while weak hydrogen-bonded water clusters were formed when the ethanol concentration increased continuously from 20%to 30%.These measurements provide new insights into the structural changes and changes in the hydration behavior of HSA,revealing the dynamic process of protein purification,and providing a theoretical basis for the selection of HSA alcoholic precipitation process parameters,as well as for further studies of complex biological systems.

Serum albumin as a prognostic predictor reflecting host immunity in patients with non-small cell lung cancer

Objective:Serum albumin(ALB)can transport nutrients to circulating and local immune cells by passing through blood vessels and has attracted attention as a prognostic predictor of non-small cell lung cancer(NSCLC)because it reflects the host immunity from peripheral blood(PBL)to the tumor microenvironment. Methods:Clinical data regarding the PBL and tumor tissues were obtained at The First Hospital of Jilin University between February 2009 and March 2017.We detected indices of glucose and lipid metabolism,classified and counted PBL lymphocytes using flow cy-tometry,determined the tumor-infiltrating lymphocytes by quantitative immunofluorescence,and analyzed the T-cell receptor(TCR)rep-ertoire by high-throughput sequencing of the TCR β-chain.The correlations between ALB and metabolic immune indices were analyzed by t tests and Pearson chi-square test. Results:A total of 211 enrolled NSCLC patients were divided into a relatively high-ALB group(>41.75 g/L,n = 56)and a low-ALB group(≤41.75 g/L,n = 155);patients with high ALB had lower Treg cells(P<0.05)and more CD8+ cytotoxic T cells in the PBL(P<0.01)and a higher proportion of stromal CD8+ tumor-infiltrating lymphocytes(P = 0.047)than patients with low ALB.High ALB was also significantly related to more diversity in the TCR repertoire(P = 0.0021,r2 = 0.5481).Moreover,ALB was identified as an in-dependent prognostic factor based on a multivariate Cox regression analysis(P = 0.032;hazard ratio(HR)= 1.804;95%confidence interval(CI)= 1.035-3.146).The median overall survival in patients with low ALB vs high ALB was 28.2 vs 42.2 months(P=0.0142),respectively.Among patients with nonmetastatic NSCLC(stage Ⅰ-Ⅲ),there was a higher incidence of distant metastasis in the low-ALB group than that in the high-ALB group(41.3%and 22.2%,P=0.043).A low ALB also had a strong association with a higher risk for disease progression(P<0.001)and death(P<0.01;HR = 0.555;95%CI= 0.312-0.988). Conclusions:Albumin could affect the host immunity,and high ALB predicted a reduced risk of distant metastasis and improved the prognosis in NSCLC patients.

Studies on Interactions of Antibiotics with Serum Albumin by Surface Plasmon Resonance Biosensor

Characterizing how chemical compounds binding to serum albumin is essential in evaluating drug candidates and is the focus of this study. A surface plasmon resonance biosenser developed in this laboratory was used to determine the binding constants of antibiotics with serum albumin. The binding constants of five antibiotics（asithromycin, spectinomycin, gentamycin, metacycline and kanamycin） with serum albumins were obtained.

(E)-2-Benzylidenecycloalkanones XII.*Kinetic Measurement of Bovine and Human Serum Albumine Interaction with Selected Chalcones and Their Cyclic Chalcone Analogues by UV Spectrophotometry

UV-VIS spectroscopic investigations of interaction of bovine and human serum albumin with selected chalcones (1) and their cyclic chalcone analogues: (E)-2-(4’-X-benzylidene-1-tetralones (3), benzosuberones (4) with dimethylamino and methoxy substituents and (E)-2-(2’,4’-dimethox- ybenzylidene)-1-indanone (2) were performed in polar respiration medium. Absorption maxima of the tested compounds were investigated in the presence of bovine and human serum albumin at the 0, 10, 30 and 60 minute timepoints of the interaction. The absorbance of all studied compounds in the presence of proteins decreased after one hour of the reaction. Molecule 4a showed the strongest and fastest kinet initial interaction with both albumins.

Postoperative decrease of serum albumin predicts shortterm complications in patients undergoing gastric cancer resection

AIM To find an accurate and simple predictor for postoperative short-term complications after gastrectomy. METHODS Two hundred and twenty-three patients undergoing gastric cancer resection between October 1,2015 and September 30,2016 were enrolled in this study. Univariate and multivariate analyses were used toidentify risk factors for complications after gastrectomy. The cutoff values and diagnostic accuracy were examined by receiver operating characteristic curves.RESULTS Sixty-two(27.8%) patients had short-term complications after gastric cancer resection. The postoperative decrease in serum albumin(?ALB) was an independent risk factor for complications(OR = 17.957,95%CI: 6.073-53.095,P < 0.001). The cutoff value was 14.0% and the area under the curve was higher than that of C-reactive protein on postoperative day 3(area under the curve: 0.806 vs 0.709). Patients with ?ALB ≥ 14.0% were more likely to have short-term complications after gastrectomy(46.7% vs 5.0%,P < 0.001),prolonged hospital stay(17.2 ± 10.8 d vs 14.1 ± 4.2 d,P = 0.007) and higher comprehensive complication index(P < 0.001) than those with ?ALB < 14.0%.CONCLUSION Postoperative ?ALB with a cutoff of 14.0% can be used to recognize patients who have high risk of short-term complications following gastric cancer resection.

Spectroscopic analysis on the binding interaction of biologically active pyrimidine derivative with bovine serum albumin

A biologically active antibacterial reagent, 2-amino-6-hydroxy-4-（4-N, N-dimethylaminophenyl）-pyr- imidine-5-carbonitrile （AHDMAPPC）, was synthesized. It was employed to investigate the binding in- teraction with the bovine serum albumin （BSA） in detail using different spectroscopic methods. It ex- hibited antibacterial activity against Escherichia cali and Staphylococcus aureus which are common food poisoning bacteria. The experimental results showed that the fluorescence quenching of model carrier protein BSA by AHDMAPPC was due to static quenching. The site binding constants and number of binding sites （n ≈ 1） were determined at three different temperatures based on fluorescence quenching results. The thermodynamic parameters, enthalpy change （AH）, free energy （AG） and entropy change （AS） for the reaction were calculated to be 15.15 kJ/mol, -36.11 kJ/mol and 51.26J/mol K according to van＇t Hoff equation, respectively. The results indicated that the reaction was an endothermic and spontaneous process, and hydrophobic interactions played a major role in the binding between drug and BSA. The distance between donor and acceptor is 2.79 nm according to Forster＇s theory. The alterations of the BSA secondary structure in the presence of AHDMAPPC were confirmed by UV-visible, synchronous fluorescence, circular dichroism （CD） and three-dimensional fluorescence spectra. All these results in- dicated that AHDMAPPC can bind to BSA and be effectively transported and eliminated in the body. It can be a useful guideline for further drug design.

Combined fluorescence and electrochemical investigation on the binding interaction between organic acid and human serum albumin

Human serum albumin （HSA） is a plasma protein responsible for the binding and transport of fatty acids and a variety of exogenous chemicals such as drugs and environmental pollutants. Such binding plays a crucial role in determining the ADME （absorption, distribution, metabolism, and excretion） and bioavailability of the pollutants. The binding interaction between HSA and acetic acid （C2）, octanoic acid （C8） and dodecanoic acid （C12） has been investigated by the combination of site-specific fluorescent probe, tryptophan intrinsic fluorescence and tyrosine electrochemistry. For the study of the fatty acid interaction with the two drug-binding sites on HSA, two fluorescent probes, dansylamide and dansyl-L-proline were employed in the displacement measurements. Intrinsic fluorescence of tryptophan in HSA was monitored upon addition of the fatty acids into HSA. Electrocatalyzed response of the tyrosine residues in HSA by a redox mediator was used to investigate the binding interaction. Qualitatively, observations from these three approaches were very similar. HSA did not show any change in the fluorescence and electrochemical experiments after mixing with C2, suggesting there is no significant interaction with the short-chain fatty acid. For C8, the measured signal dropped in a single-exponential mode, indicating an independent and non-cooperative binding. The calculated association constant and binding ratio were 3.1 × 10^6 L/mol and 1 with drug binding Site Ⅰ, 1.1 × 107 L/mol and 1 with Site Ⅱ, and 7.0× 0^4 L/mol and 4 with the tryptophan site, respectively. The measurements with C12 displayed multiple phases of fluorescence change, suggesting cooperativity and allosteric effect of the C12 binding. These results correlate well with those obtained by the established methods, and validate the new approach as a viable tool to study the interactions of environmental pollutants with biological molecules.

Investigation of the interaction between indigotin and two serum albumins by spectroscopic approaches

The binding characteristics of indigotin with human serum albumin （HSA） and bovine serum albumin （BSA） have been investigated by various spectroscopic techniques. Spectroscopic analysis revealed that the quenching mechanism between indigotin and HSA/BSA belonged to the static quenching. The displacement experiments suggested that indigotin primarily bound to tryptophan residues on proteins within site I. The thermodynamic parameters indicated that the binding of indigoti^HSA/BSA mainly depended on the hydrophobic interaction. The binding distance of indigotin to HSA/BSA was evaluated. The results by synchronous fluorescence, three- dimensional fluorescence, Fourier Transform Infrared spectroscopy （FT-IR） and circular dichroism （CD） spectra showed that the conformation of proteins altered in the presence of indigotin.

Immobilization of Bovine Serum Albumin on Poly(ether ether ketone) for Surface Biocompatibility Improvement

UV-induced graft polymerization of acrylic acid（AA） on poly（ether ether ketone）（PEEK） films was carried out to introduce ―COOH for the subsequent immobilization of bovine serum albumin（BSA）.BSA was introduced on PEEK surface based on the condensation reaction between ―NH 2 and ―COOH.The modified surface（PEEK-BSA） was characterized by energy-disperse spectrometry（EDS）,X-ray photoelectron spectroscopy（XPS）,water contact angle measurement and UV spectrum analysis.The contact angle was found to decrease from 104° for the virgin PEEK films to 63° for the BSA-immobilized PEEK films,demonstrating a significant improvement of surface hydrophilicity.Moreover,the appearance of nitrogen on PEEK film confirmed by XPS and EDS indicates the immobilization of BSA on PEEK surface.

Sonocatalytic Damage of Bovine Serum Albumin (BSA) in the Presence of Nanometer Titanium Dioxide (TiO_2) Catalyst

The sonocatalytic damage of bovine serum albumin （BSA） was studied in the presence of nanometer titanium dioxide （TiO2） powders by low frequency （80 kHz） ultrasound. The destruction of secondary structure and change of α-helical structure of BSA were reflected by ultraviolet （UV） and circular dichroism （CD） spectroscopies.

Synthesis of Metal Porphyrins Tailed with Salicylic Acid and their Interaction with Bovine Serum Albumin

A synthetic method of porphyrins tailed with salicylic substituents is described. Reaction of bromoalkoxyphenyl porphyrin 1 with salicylic acid gave porphyrins 2~5. These new compounds were confirmed by 1H NMR, IR, UV-vis, MS and elemental analysis, and observed their interaction with bovine serum albumin (BSA) in fluorescence spectrum.

Determination of Enantiomeric Compositions of Tryptophan by Chemometric Analysis of the Fluorescence Spectra of Bovine Serum Albumin Receptor-ligand Mixtures

In this work, a novel method was constructed to determine the enantiomeric composition of tryptophan （Trp） by bovine serum albumin （BSA） based on the fluorescence spectra of the receptor-ligand mixtures coupled with partial least squares （PLS-1） analysis. As a result the enantiomeric composition of Trp was accurately determined.

Thermodynamic study on the interaction between anti-tumor drug tegafur and human serum albumin

The changes of thermodynamic properties of the system on interaction between tegafur and human serum albumin （HSA） and the changes of secondary structure units of HSA in the system at 298.15 K have been investigated by the Nano-Watt-Scale isothermal titration calorimetry （ITC）, the Langmuirs binding model and the circular dichroism （CD） spectrometry.

Characterization of Interaction Between Raltitrexed and Bovine Serum Albumin by Optical Spectroscopic Techniques

The interaction of raltitrexed（RTX） with bovine serum albumin（BSA） was investigated by steady state/lifetime fluorescence spectroscopy and circular dichroism（CD） spectroscopy under the simulative physiological conditions.The results of fluorescence titration reveal that RTX could strongly quench the intrinsic fluorescence of BSA via a static quenching procedure.The obtained binding constant K A of RTX with BSA was 478630 and 44259 L/mol at 298 and 310 K,respectively.According to van＇t Hoff equation,the thermodynamic parameters ΔH,ΔG and ΔS were calculated,indicating that hydrophobic forces were the predominant intermolecular forces in stabilizing the complex.The binding process was a spontaneous process,in which Gibbs free energy change was negative.According to F rster＇s non-radioactive energy transfer theory,the distance r between donor（BSA） and acceptor（RTX） was 3.82 nm,suggesting that the energy transfer from BSA to RTX occurred with high probability.Displacement experiment and the number of binding sites calculation confirmed that RTX could bind to the site-I of BSA.Furthermore,the effects of pH and some metal ions on the interaction of RTX with BSA were also investigated.The results of synchronous fluorescence and CD spectra show that the RTX-BSA binding induced conformational changes in BSA.

Investigation on the differences of four flavonoids with similar structure binding to human serum albumin

Flavonoids are structurally diverse and the most ubiquitous groups of polyphenols distributed in the various plants,which possess intensive biological activities.In this study,the interaction mechanisms between four flavonoids containing one glucose unit with similar molecular weight isolated from the Tibetan medicinal herb Pyrethrum tatsienense,namely.apigenin-7-O-β-D-glucoside（1）,luteolin-7-O-β-D-glucoside（2）.quercetin-7-O-β-D-glucoside（3）.quercetin-3-O-β-D-glycoside（4）.and human serum albumin（HSA）,were investigated by fluorescence.UV-vis absorbance,circular dichroism,and molecular modeling.The effects of biological metal ions Mg2＋,Zn2＋,and Cu2＋ on the binding affinity between flavonoids and HSA were further examined.Structure-activity relationships of four flavonoids binding to HSA were discussed in depth and some meaningful conclusions have been drawn by the experiment data and theoretical simulation.In addition,an interesting phenomenon was observed that the microenvironment of the binding site I in HSA has hardly changed in the presence of 4 differentiating from the other three flavonoids on the basis of conformation investigations.

Characterization of Gallic Acid Interaction with Human Serum Albumin by Spectral and Molecular Modeling Methods

The binding of drugs with human serum albumin（HSA） is a crucial factor influencing the distribution and bioactivity of drugs in the body.To understand the action mechanisms between gallic acid（GA,3,4,5-trihydroxybenzoic acid） and HSA,the binding of GA with HSA was investigated by a combined experimental and computational approach.The fluorescence properties of HSA and the binding parameters of GA collectively indicate that the binding is characterized by static quenching mechanism at one high affinity binding site.According to the estimated molecular distance between the donor（HSA） and the acceptor（GA）,the binding is related to the fluorescence resonance energy transfer.As indicated by the thermodynamic parameters,hydrophobic interaction plays a major role in the GA-HSA complex.Further,the experimental results reveal that GA is bound in the large hydrophobic cavity of subdomain IIA in the site I of HSA,which is well approved by molecular docking.

Comprehensive overview of human serum albumin glycation in diabetes mellitus

The presence of excess glucose in blood is regarded as a sweet hurt for patients with diabetes.Human serum albumin(HSA)is the most abundant protein in human plasma,which undergoes severe non-enzymatic glycation with glucose in patients with diabetes;this modifies the structure and function of HSA.Furthermore,the advanced glycation end products produced by glycated HSA can cause pathological damage to the human body through various signaling pathways,eventually leading to complications of diabetes.Many potential glycation sites on HSA have different degrees of sensitivity to glucose concentration.This review provides a comprehensive assessment of the in vivo glycation sites of HSA;it also discusses the effects of glycation on the structure and function of HSA.Moreover,it addresses the relationship between HSA glycation and diabetes complications.Finally,it focuses on the value of non-enzymatic glycation of HSA in diabetes-related clinical applications.

Study on a noninvasive method for rapid screening Human Serum albumin injectables by Raman spectroscopy

Human serum albumin(HSA)injectable product is a severely afflicted area on drug safety due to its high price and restricted supply.Raman spectroscopy performances high specificity on HSA detection and it is even possible to determine HSA injectable products noninvasively.In this study,we developed a noninvasive rapid screening method for of HSA injectable products by using portable Raman spectrometer.Qualitative models were established by using principal component analysis combined with classical least squares(PCA-CLS)algorithm,while quanti-tative model was established by using partial least squares(PLS)algorithm.Model transfer in different instruments of both the same and different apparatus modules was further discussed in this paper.A total of 34 HSA injectable samples collected from markets were used for verification.The identification results showed 100%accuracy and the predicted concentrations of those identified as true HSA were consistent with their labeled concentrations.The quantitative results also indicated that model transfer was excellent in the same apparatus modules of Raman spectrometer at all concentration levels,and still good enough in the different apparatus modules although the relative standard deviation(RSD)value showed a little increasing trend at low HSA concentration level.In conclusion,the method was proved to be feasible and efficient for screening HSA injections,especially on its screening speed and the consideration of glass containers.Moreover,with inspiring results on the model transfer,the method could be used as a universal screening mean to different Raman instruments.