Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia:Based on serum pharmacochemistry and network pharmacology

Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.

Integrated network pharmacology and metabolomics to explore the mechanisms of Shenzao dripping pill against chronic myocardial ischemia

Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic effects.The objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat model.Methods:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of SZDP.The integration of network pharmacology and metabolomics was conducted to investigate the mechanisms.Molecular docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated targets.Results:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart damage.Metabolomics results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for CMI.Integrating network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl formamidocarboxamide.Conclusion:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.

Preoperative Serum Albumin Levels and Postoperative Acute Kidney Injury in Off-Pump Coronary Artery Bypass Surgery: A Single-Center Study in Bangladesh

Background: Serum albumin, a vital plasma protein, helps maintain intravascular colloidal osmotic pressure, cardiac output, and renal function. Low preoperative serum albumin is linked to poor outcomes, including acute kidney injury (AKI), after off-pump coronary artery bypass (OPCAB) surgery. This study aimed to assess the relationship between preoperative serum albumin levels and early postoperative renal injury. Methods: This prospective comparative cross-sectional study was conducted from August 2019 to February 2021 at the National Heart Foundation Hospital & Research Institute, Bangladesh. It included 160 adult patients with normal preoperative renal function undergoing OPCAB. Patients were divided into two groups: Group A (serum albumin ≥ 4.0 gm/dl) and Group B (serum albumin Results: Preoperative serum albumin was significantly different between groups (Group A: 4.21 ± 0.05 gm/dl, Group B: 3.69 ± 0.04 gm/dl, p = 0.028). Group B had a higher incidence of hypertension (71.25% vs. 51.25%, p st and 3rd postoperative days were higher in Group B (p th day. Postoperative AKI occurred in 18.75% of Group A and 36.25% of Group B. Multivariate regression indicated that low preoperative serum albumin is an independent risk factor for postoperative AKI (p = 0.012, OR = 1.815, CI: 0.675 - 1.162). Conclusion: Preoperative serum albumin level is a valuable predictor of postoperative renal function. Ensuring high normal serum albumin levels before surgery can help minimize the risk of postoperative AKI.

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.

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.

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.

Research Status of Serum Pharmacology and Serum Pharmacochemistry of Traditional Chinese Medicine

Serum pharmacochemistry of traditional Chinese medicine has become a more accurate and rapidly developing reasonable way to analyze the effective material basis of traditional Chinese medicine in recent years. Through this method, we can select very complex Chinese medicine components and clarify the effective substances consistent with the main functions, and then separate and purify effective ingredients in traditional Chinese medicine, so as to explain the material basis of the drug effect and prove the rationality and principle of action of Chinese medicine compounds. It can show the multi-component and multi-target characteristic of traditional Chinese medicine, and after analyzing the migrating components of serum, we can explore the direct effective substances that act on the patient’s body, so as to accelerate and accurately complete the in-depth study of the effective substances of Chinese medicine.

Epicatechin attenuates lead(Pb)-induced cognitive impairment in mice:regulation on Nrf2 signaling pathway,and interference on the interaction between Pb with albumin

Epicatechin(EC)was used in this study to antagonize the cognitive dysfunction caused by lead(Pb)exposure in mice.Eight-week-old male Kunming mice were treated with PbCl_(2)(20 mg/kg)and/or EC(50 mg/kg)by gavage administration for 4 weeks.Morris water maze test showed that EC could improve memory dysfunction induced by Pb.EC antagonized Ca^(2+)overload,activated Nrf2 signaling pathway and reduced the accumulation of Pb in the brain and serum,which suggested that EC might alter Pb distribution in mice.In vitro,spectroscopic analysis,potentiometric titration and docking studies were applied to inquiry into the interaction between bovine serum albumin(BSA)and Pb^(2+)in presence or absence of EC.EC was proved to chelate Pb^(2+)and reduced the interaction between BSA and Pb^(2+).In summary,EC might protect Pb-induced cognitive impairment by activating Nrf2 signaling pathway,and suppressing Pb accumulation via interference on the binding of Pb to albumin.

Interaction Between Gatifloxacin and Bovine Serum Albumin

Aim To study the reaction mechanism between gatifloxacin and bovine serumalbumin (BSA) at different pHs. Methods Fluorescence spectra and UV absorbance spectra were used.Results The binding constants were determined from a double reciprocal Lineweaver-Burk curves atdifferent pHs. The binding distance r under normal physiological condition was obtained according toFoster theory of non-radiative energy transfer. The binding force between gatifloxacin and BSA wasinferred by thermody-namical coordination. Conclusion The interaction between gatifloxacin and BSAseems to be strong and the main binding force is electrostatic force.

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.

Multi-spectroscopic characterization of bovine serum albumin upon interaction with atomoxetine

The quenching interaction of atomoxetine(ATX) with bovine serum albumin(BSA) was studied in vitro under optimal physiological condition(pH=7.4) by multi-spectroscopic techniques. The mechanism of ATX-BSA system was a dynamic quenching process and was confirmed by the fluorescence spectra and lifetime measurements. The number of binding sites, binding constants and other binding characteristics were computed. Thermodynamic parameters ΔH^0 and ΔS^0 indicated that intermolecular hydrophobic forces predominantly stabilized the drug-protein system. The average binding distance between BSA and ATX was studied by F?rsters theory. UV-absorption, Fourier transform infrared spectroscopy(FT-IR), circular dichroism(CD), synchronous spectra and three-dimensional(3D) fluorescence spectral results revealed the changes in micro-environment of secondary structure of protein upon the interaction with ATX. Displacement of site probes and the effects of some common metal ions on the binding of ATX with BSA interaction were also studied.

Correlation of serum albumin and prognostic nutritional index with outcomes following pancreaticoduodenectomy

BACKGROUND Pancreaticoduodenectomy(PD) is a complex surgical procedure with a high morbidity rate. The serious complications are major risk factors for poor longterm surgical outcome. Studies have reported an association between early postoperative prognostic nutritional index(PNI) and prediction of severe complications after abdominal surgery. However, there have been no studies on the use of early postoperative PNI for predicting serious complications following PD.AIM To analyze the risk factors and early postoperative PNI for predicting severe complications following PD.METHODS We retrospectively analyzed 238 patients who underwent PD at our hospital between January 2007 and December 2017. The postoperative complications were classified according to the Dindo-Clavien classification. Grade Ⅲ-Ⅴ postoperative complications were classified as serious. The risk factors for serious complications were analyzed by univariate analysis and multivariate logistic regression analysis.RESULTS Overall complications were detected in 157 of 238 patients(65.9%) who underwent PD. The grade Ⅲ-Ⅴ complication rate was 26.47%(63/238 patients).The mortality rate was 3.7%(9/238 patients). Multivariate logistic regression analysis revealed that preoperative serum albumin [odds ratio(OR): 0.883, 95%confidence interval(CI): 0.80-0.96; P < 0.01] and PNI on postoperative day 3 <40.5(OR: 2.77, 95%CI: 1.21-6.38, P < 0.05) were independent factors associated with grade Ⅲ-Ⅴ postoperative complications.CONCLUSION Perioperative albumin is an important factor associated with serious complications following PD. Low early postoperative PNI(< 40.5) is a predictor for serious complications.

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.

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.

Significance of functional hepatic resection rate calculated using 3D CT/^(99m)Tc-galactosyl human serum albumin singlephoton emission computed tomography fusion imaging

AIM: To evaluate the usefulness of the functional hepatic resection rate (FHRR) calculated using 3D computed tomography (CT)/99mTc-galactosyl-human serum albumin (GSA) single-photon emission computed tomography (SPECT) fusion imaging for surgical decision making.METHODS: We enrolled 57 patients who underwent bi- or trisectionectomy at our institution between October 2013 and March 2015. Of these, 26 patients presented with hepatocellular carcinoma, 12 with hilar cholangiocarcinoma, six with intrahepatic cholangiocarcinoma, four with liver metastasis, and nine with other diseases. All patients preoperatively underwent three-phase dynamic multidetector CT and 99mTc-GSA scintigraphy. We compared the parenchymal hepatic resection rate (PHRR) with the FHRR, which was defined as the resection volume counts per total liver volume counts on 3D CT/99mTc-GSA SPECT fusion images.RESULTS: In total, 50 patients underwent bisectionectomy and seven underwent trisectionectomy. Biliary reconstruction was performed in 15 patients, including hepatopancreatoduodenectomy in two. FHRR and PHRR were 38.6 ± 19.9 and 44.5 ± 16.0, respectively; FHRR was strongly correlated with PHRR. The regression coefficient for FHRR on PHRR was 1.16 (P < 0.0001). The ratio of FHRR to PHRR for patients with preoperative therapies (transcatheter arterial chemoembolization, radiation, radiofrequency ablation, etc.), large tumors with a volume of > 1000 mL, and/or macroscopic vascular invasion was significantly smaller than that for patients without these factors (0.73 ± 0.19 vs 0.82 ± 0.18, P < 0.05). Postoperative hyperbilirubinemia was observed in six patients. Major morbidities (Clavien-Dindo grade ≥ 3) occurred in 17 patients (29.8%). There was no case of surgery-related death.CONCLUSION: Our results suggest that FHRR is an important deciding factor for major hepatectomy, because FHRR and PHRR may be discrepant owing to insufficient hepatic inflow and congestion in patients with preoperative therapies, macroscopic vascular invasion, and/or a tumor volume of > 1000 mL.

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 binding behavior of human serum albumin and phosphorothioate oligodeoxynucleotide

Aim To study the binding behavior between human serum albumin （HSA） and phosphorothioate oligodeoxynucleotide （PS- ODN） and the effects of bivalent cations on the interaction. Methods Surface plasma resonance, circular dichroism and fluorescence experiments were conducted. Results （ 1 ） the binding ability was decreased along with the increase of pH; （2） Zn^2＋and Ni^2＋ enhanced the interaction between PS-ODN and HSA; （3） Upon PS-ODN binding, the conformation of HSA was changed with an increase of β - sheet. Conclusion The results provide experimental evidences to the hypothesis that PS-ODN binds with HSA in the positive potential region, and histidine residues located in the region play a crucial rule in the interaction.

Study of <i>in Vitro</i>Interaction of Sildenafil Citrate with Bovine Serum Albumin by Fluorescence Spectroscopy

In vitro interaction of sildenafil citrate (SC) with bovine serum albumin (BSA) was investigated at two excitation wavelengths of BSA (280 nm and 293 nm) at two different temperatures (298 K and 308 K) by fluorescence emission spectroscopy. The study showed that quenching of BSA fluores-cence by sildenafil citrate was the result of formation BSA-SC complex with probable involvement of both tryptophan and tyrosine residues of BSA. Fluorescence quenching constant was determined from Stern-Volmer equation, and both static quenching and dynamic quenching were showed for BSA by SC at the conditions. Van’t Hoff equation was used to measure the thermodynamic parameters ΔG, ΔH, and ΔS at the temperatures which indicated that the hydrogen bond and the hydrophobic forces played major roles for BSA-SC complexation. The binding number (n) was found to be ≈1 indicating that one mole BSA bound with one mole SC. The binding affinity of SC to BSA was calculated at different temperatures. The binding constant was decreased with increasing temperatures indicating that stability of BSA-SC complex decreased with increasing temperatures.

Insight into the interaction of inhaled corticosteroids with human serum albumin: A spectroscopic-based study

It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein unbound, and active ICS can cause systemic adverse effects. Therefore, a detailed investigation of drug-protein interaction could be of great interest to understand the pharmacokinetic behaviour of corticosteroids and for the design of new analogues with effective pharmacological properties. In the present work, the interaction between some corticosteroids and human serum albumin(HSA) has been studied by spectroscopic approaches. UV–Vis spectroscopy confirmed that all the investigated corticosteroids can bind to HSA forming a protein-drug complex. The intrinsic fluorescence of HSA was quenched by all the investigated drugs, which was rationalized in terms of a static quenching mechanism. The thermodynamic parameters determined by the Van't Hoff analysis of the binding constants(negative ΔH and ΔS values) clearly indicate thathydrogen bonds and van der Waals forces play a major role in the binding process between albumin and betamethasone, flunisolide and prednisolone, while hydrophobic forces may play a major role in stabilizing albumin-triamcinolone complexes.