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This article delves into the interaction between HSA protein and synthesized platinum complexes, with formula: [Pt(Propyl-NH2)2(Propylglycine)]NO3 and [Pt(Tertpentyl-NH2)2(Tertpentylglycine)]NO3, through a range of methods, including spectroscopic (UV-visible, fluorescence, synchronous fluorescence and CD) analysis and computational modeling (molecular docking and MD simulation). The binding constants, the number of binding sites, and thermodynamic parameters were obtained at 25 to 37 °C. The study found that both complexes could bind with HSA (moderate affinity for Tertpentyl and strong affinity for Propyl derivatives) and occupied one binding site in HSA (validated with, Stern-Volmer, Job-plots, and molecular docking investigations) located in subdomain IIA. The binding mechanisms of both mentioned Pt(II) agents were different, with the Propyl derivative predominantly using van der Waals forces and hydrogen bond interactions with a static quenching mechanism and the Tertpentyl derivative mainly utilizing hydrophobic force with a dynamic quenching mechanism. However, the two ligands affected protein differently; the Tertpentyl complex did not significantly alter the protein structure upon binding, as evidenced by synchronous fluorescence spectroscopy (SFS), CD spectroscopy, and MD analysis. The outcome helps in understanding the binding mechanisms and structural modifications induced by the ligands, which could aid in the innovation of more effective and stable Pt(II)-based drugs.
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Glicina , Simulação de Acoplamento Molecular , Ligação Proteica , Albumina Sérica Humana , Termodinâmica , Humanos , Glicina/química , Glicina/análogos & derivados , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Sítios de Ligação , Simulação de Dinâmica Molecular , Espectrometria de Fluorescência , Ligantes , Platina/químicaRESUMO
PURPOSE: This study aimed to determine if Ki-67, a commonly used marker to measure tumor proliferation, is a reliable prognostic factor in various types of gastrointestinal (GI) cancers based on current high-quality multivariable evidence. METHODS: A comprehensive search was conducted in PubMed, Embase, Scopus, and ISI Web of Science databases to investigate the association between Ki-67 positivity and overall survival (OS) and disease/recurrence-free survival (DFS/RFS) in GI cancers. Heterogeneity was assessed using Chi-square-based Q and I2 analyses and publication bias using funnel plots and Egger's analysis. In addition, Ki-67 levels in different GI cancers were examined by different platforms. The prognostic capability of Ki-67, gene ontology (GO), and pathway enrichment analysis were obtained from GEPIA2 and STRING. RESULTS: Totally, 61 studies, involving 13,034 patients, were deemed eligible for our evaluation. The combined hazard ratios (HRs) demonstrated the prediction ability of overexpressed Ki-67 for a worse OS (HR: 1.67, P < 0.001; HR: 1.37, P = 0.021) and DFS/RFS (HR: 2.06, P < 0.001) in hepatocellular and pancreatic malignancies, respectively, as confirmed by multi-omics databases. However, similar correlation was not found in esophageal, gastric, and colorectal cancers. Furthermore, most of the associations were identified to be robust based on different subcategories and publication bias assessment. Finally, enriched Ki-67-related genes were found to be involved in various important signaling pathways, such as cell cycle, P53 signaling network, and DNA damage responses. CONCLUSION: This study supports that Ki-67 can serve as an independent prognostic biomarker for pancreatic and hepatocellular malignancies in clinical settings.
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Biomarcadores Tumorais , Neoplasias Gastrointestinais , Antígeno Ki-67 , Humanos , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análise , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/genética , Prognóstico , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , MultiômicaRESUMO
This paper focuses on the synthesis of nano-oxali-palladium coated with turmeric extract (PdNPs) using a green chemistry technique based on the reduction in the Pd (II) complex by phytochemicals inherent in turmeric extract. PdNPs were examined and characterized using Field Emission Scanning Electron Microscopy (FESEM), Dynamic Light Scattering (DLS), Fourier Transform Infrared (FTIR), and Atomic Force Microscopy (AFM). Using different spectroscopic and molecular dynamics simulations, a protein-binding analysis of the produced nanoparticle was conducted by observing its interaction with human serum albumin (HSA). Lastly, the cytotoxic effects and apoptotic processes of PdNPs were studied against the HCT116 human colorectal cell line using the MTT assay and flow cytometry tests. According to the findings, PdNPs with spherical and homogenous morphology and a size smaller than 100 nm were generated. In addition, they can induce apoptosis in colorectal cancer cells in a dose-dependent manner with a lower Cc50 (78 µL) than cisplatin and free oxali-palladium against HCT116 cells. The thermodynamic characteristics of protein binding of nanoparticles with HSA demonstrated that PdNPs had a great capacity for quenching and interacting with HSA through hydrophobic forces. In addition, molecular dynamics simulations revealed that free oxali-palladium and PdNP attach to the same area of HSA via non-covalent interactions. It is conceivable to indicate that the synthesized PdNPs are a potential candidate for the construction of novel, nature-based anticancer treatments with fewer side effects and a high level of eco-friendliness.
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Neoplasias Colorretais , Nanopartículas , Oxalidaceae , Humanos , Ligação Proteica , Paládio , Apoptose , Neoplasias Colorretais/tratamento farmacológicoRESUMO
Lead is a widespread environmental hazard that can adversely affect multiple biological functions. Blood cells are the initial targets that face lead exposure. However, a systematic assessment of lead dynamics in blood cells at single-cell resolution is still absent. Herein, C57BL/6 mice were fed with lead-contaminated food. Peripheral blood was harvested at different days. Extracted red blood cells and leukocytes were stained with 19 metal-conjugated antibodies and analyzed by mass cytometry. We quantified the time-lapse lead levels in 12 major blood cell subpopulations and established the distribution of lead heterogeneity. Our results show that the lead levels in all major blood cell subtypes follow lognormal distributions but with distinctively individual skewness. The lognormal distribution suggests a multiplicative accumulation of lead with stochastic turnover of cells, which allows us to estimate the lead lifespan of different blood cell populations by calculating the distribution skewness. These findings suggest that lead accumulation by single blood cells follows a stochastic multiplicative process.
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Chumbo , Longevidade , Animais , Camundongos , Chumbo/toxicidade , Camundongos Endogâmicos C57BL , Leucócitos , EritrócitosRESUMO
In this study, we have successfully synthesized magnetic Fe3O4 nanoparticles adorned with samarium (Sm-MNPs) utilizing ginger extract for the very first time. Furthermore, a comprehensive characterization of the nanoparticles along with an exploration of their physicochemical attributes was conducted. The biological functionalities of the synthesized nanoparticles were investigated through a thorough examination of their interaction with calf thymus DNA (ctDNA) using diverse spectroscopic techniques encompassing ultraviolet-visible (UV-Vis) and fluorescence spectroscopy at varying temperatures. Subsequently, we evaluated the cytotoxicity of the magnetic nanoparticles using a colorectal cancer cell model (HCT116 cells) and a tetrazolium colorimetric assay (MTT assay). The characterization of the ginger extract-coated magnetic nanoparticles (ginger-Sm-MNPs) revealed their superparamagnetic nature, nanocrystalline structure, spherical morphology, hydrodynamic size of 155 nm, and uniform distribution. The outcomes from UV-Vis and fluorescence spectroscopy affirmed the binding of ginger-Sm-MNPs with ctDNA. Additionally, the MTT assay demonstrated that the cytotoxicity of ginger-Sm-MNPs surpassed that of both magnetite nanoparticles and ginger extract. Notably, the inhibitory concentrations (IC50) for the green-synthesized nanoparticles after 24 and 48 h of incubation were determined as 198.1 and 135.8 µg/mL, respectively. In conclusion, our study findings suggest the potential utility of ginger-Sm-MNPs as a promising candidate for various biomedical applications.Communicated by Ramaswamy H. Sarma.
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A biosensor based on glutamate oxidase (GluOx) was developed to measure glutamate concentration. The main function of this type of biosensor is related to the structure and catalytic activity of GluOx. Since radiofrequency, as the widest spectrum of electromagnetic fields, can affect the catalytic activity and structure of GluOx, in this study, the effect of these fields on the analytical parameters of the fabricated biosensor was investigated. To build the biosensor a sol-gel solution of chitosan and native GluOx were prepared and then immobilized on the surface of the platinum electrode. Similarly, to investigate the effect of radiofrequency fields on the analytical parameters of the biosensor, instead of the native GluOx, irradiated GluOx was used to build the biosensor. To evaluate the biosensor responses, cyclic voltammetry experiments were performed and voltammograms were considered as biosensor responses. To determine the analytical parameters including detection limit, linear range, and saturation region of the responses, calibration curves were drawn for each of the biosensors. Also the long-term stability and selectivity of the fabricated biosensor were evaluated. Thereafter, the optimum pH and temperature for each of these two biosensors were examined. The results showed that radiofrequency waves harmed the detection and response of biosensors in the saturation region, while they had little effect on the linear region. Such results could be due to the effect of radiofrequency waves on the structure and function of glutamate oxidase. In general, the results indicate that when a glutamate oxidase-based biosensor is used to measure glutamate in radiofrequency fields, corrective coefficients for this type of biosensor should be considered to accurately measure glutamate concentration.
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Multilayered pH-responsive hollow microcapsules with non-toxicity and biological specificity advantages were prepared from two kinds of polymers i.e., chitosan (CH) and poly (ethylene glycol dimethacrylate-co-methacrylic acid) (PE) via layer-by-layer (LbL) method, which is followed by subsequent removal of silica core. The hollow nature of obtained spherical microcapsules was found by transmission electron microscopy (TEM). The microcapsules were prepared as gemcitabine (GM) and curcumin (CR) carriers. The drugs have been loaded within the microcapsules during or after the synthetic procedure. Although acceptable loading efficiencies (LE) were obtained in both methods, the amount of drug loaded during the synthesis method is relatively higher. Values above 78% and 87%, for releasing efficiency (RE%) and encapsulation efficiency (EE%), respectively, demonstrate the high potential of the prepared microcapsules for drug delivery. In addition, the difference between the amount of drug released in acidic and neutral pH indicates the pH-responsivity of the prepared microcapsules. Moreover, the dose-dependent high cytotoxicity effect of the prepared microcapsules was observed on the HCT116 colorectal carcinoma cells.
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Quitosana , Sistemas de Liberação de Medicamentos , Cápsulas/química , Microscopia Eletrônica de Transmissão , Quitosana/química , Polímeros/química , Portadores de Fármacos/químicaRESUMO
Since the urease enzyme creates gastric cancer, peptic ulcer, hepatic coma, and urinary stones in millions of people worldwide, it is essential to find strong inhibitors to help patients. Natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients, the so-called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, and cosmetic applications. Kaempferol (KPF) is an antioxidant found in many fruits and vegetables. Many reports have explained the significant effects of dietary KPF in reducing the risk of chronic diseases such as cancer, ischemia, stroke, and Parkinson's. The current study aimed at investigating the inhibitory impact of KPF on Jack bean urease (JBU) using molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations to confirm the results obtained from isothermal titration calorimetry (ITC), extended solvation model, and docking software. In addition, UV-VIS spectrophotometry was used to study the kinetics of urease inhibition. Calorimetric and spectrophotometric determinations of the kinetic parameters of this inhibition indicate the occurrence of a reversible and noncompetitive mode. Also, the docking and MD results indicated that the urease had well adapted to the kaempferol in the binding pocket, thereby forming a stable complex. Kaempferol displayed low binding energy during MMPBSA calculations. The inhibitory potential of kaempferol was confirmed by experimental and simulation data, but in vivo investigations are also recommended to validate our results.
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PURPOSE: Bee Venom (BV) has been used to treat rheumatoid arthritis (RA) for many centuries. However, its clinical use is limited by pain and fear of bee stings/injection. Nanoemulsions (NEs) are nanocarriers that are able to help their content(s) penetrate through the skin. They also act as drug reservoirs on the skin to provide an efficient, sustained-release vehicle. METHODS: In this paper, we present the development of a stable water-in-oil NE to help passing BV through the animal skin when used topically. RESULTS: Particle size of NE was 12.7 to 29.8 nm for NEs containing 0 to 150 µg/ml BV. Also, its anti-inflammatory effects were evaluated in rat models of type II collagen-induced arthritis. Topical administration of NEs containing 18.75 or 9.37 µg/ml BV were able to significantly (p < 0.05) reduce inflammation in the rat paws compared to the blank and control groups. CONCLUSION: Our findings demonstrated the efficacy of NEs containing BV to reduce inflammation caused by RA animal model.
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Artrite Experimental , Artrite Reumatoide , Venenos de Abelha , Mordeduras e Picadas de Insetos , Animais , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Venenos de Abelha/farmacologia , Venenos de Abelha/uso terapêutico , Mordeduras e Picadas de Insetos/tratamento farmacológico , Dor/tratamento farmacológico , RatosRESUMO
We investigated the potential carrier of milk beta-casein (ß-CN) and its interactions with 5-fluorouracil (5-FU) and iron oxide nanoparticles (Fe3O4 NPs). We used different spectroscopic methods of fluorescence, UV-Visble, circular dichroism (CD), synchronous fluorescence, zeta potential assay, and computational studies to clarify the protein interaction with 5-FU and Fe3O4 NPs. The fluorescence data indicated both Fe3O4 NPs and 5-FU could quench the intrinsic fluorescence of ß-CN. Fluorescence measurements showed that the single interaction of ß-CN with 5-FU or Fe3O4 NPs was static, while reacted ß-CN with both 5-FU and Fe3O4 NPs simultaneously showed a dynamic quenching. Synchronous fluorescence data in both tests revealed that the tryptophan (Trp) residue of ß-CN had a dominant role in quenching and the polarity of its microenvironment more than tyrosine (Tyr) increased in interaction with 5-FU. All the binding sites and thermodynamic parameters were obtained at 25, 37, and 42 °C. The analysis of thermodynamic parameters and Job's plot techniques pointed to that both of these complexes with the 1:1 M ratio were exothermic (ΔH°<0) driven with the van der Waals and H-bonding interactions (in agreement with the docking results). The CD spectra in the region of far-UV and thermal denaturation study indicated minor changes in the secondary structure of ß-CN in the presence of various concentrations of Fe3O4 NPs and 5-FU. Also, from the molecular dynamics (MD) analysis, as a result, the protein structure was stable during 100 ns. The outcomes highlighted that ß-CN protein could form a great bind with 5-FU and Fe3O4 NPs ligands (supporting the zeta potential assay results) by independent binding sites. These results would be helpful insight to construct a potential magnetic nanocarrier ß-CN base for 5-FU drug delivery.
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Caseínas , Nanopartículas , Sítios de Ligação , Dicroísmo Circular , Fluoruracila , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Espectrometria de Fluorescência , TermodinâmicaRESUMO
MicroRNAs (miRNAs), as the small, non-coding, evolutionary conserved, and post-transcriptional gene regulators of the genome, have been highly associated with various diseases such as cancers, viral infections, and cardiovascular diseases. Several techniques have been established to detect miRNAs, including northern blotting, real-time polymerase chain reaction (RT-PCR), and fluorescent microarray platform. However, it remains a significant challenge to develop sensitive, accurate, rapid, and cost-effective methods to detect miRNAs due to their short size, high similarity, and low abundance. The electrochemical biosensors exhibit tremendous potential in miRNA detection because they satisfy feature integration, portability, mass production, short response time, and minimal sample consumption. This article reviewed the working principles and signal amplification strategies of electrochemical DNA biosensors summarized the recent improvements. With the development of DNA nanotechnology, nanomaterials and biotechnology, electrochemical DNA biosensors of high sensitivity and specificity for microRNA detection will shortly be commercially accessible.
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The abuse application of glyphosate can result in a potential hazard for environment and human, however its ultrasensitive detection remains challenging. Herein, a Cu2+ modulated DNA-templated silver nanoclusters (DNA-AgNCs) sensor was constructed to sensitively determine glyphosate based on the turn-on fluorescence strategy. The fluorescence quenching of DNA-AgNCs occurred with the existence of Cu2+. Upon the presence of glyphosate, the functional groups on the surface of glyphosate could chelate with Cu2+, following the fluorescence recovery of DNA-AgNCs. Through the stoichiometric methods, we unveil that Cu2+-trigged fluorescence quenching mode is a combination of static and dynamic quenching with the static mode being predominant. In DNA-AgNCs/Cu2+ system, the carboxylate, amine, and phosphonate groups of glyphosate interact with Cu2+ through chelation, in which the carboxylate oxygen, the phosphonate oxygen atoms, and the monoprotonated secondary amine nitrogen atom and Cu2+ form chelate rings. This fluorescence sensor showed a desired linearity of glyphosate analysis under the optimum conditions, ranging from 15 to 100 µg/L with a low detection down to 5 µg/L. Moreover, the proposed sensor was successfully utilized to measure glyphosate in real samples, indicating a promising application in pesticide residues detection.
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Nanopartículas Metálicas , Prata , DNA/genética , Glicina/análogos & derivados , Humanos , GlifosatoRESUMO
Cisplatin is a widely used anti-cancer drug which inhibits the replication and polymerization of DNA molecule while showing some side effects and drug resistance. For this reason, to enhance its therapeutic index, researchers have synthesized several thousand analogs and tested their properties. In this project, several cisplatin analogs were designed to theoretically study the biological activity and lipophilicity effects on amine changes. The amines of the cisplatin molecule were substituted with aliphatic amines in different analogs. Computational methods such as molecular dynamics simulation, molecular docking, and molecular mechanics Poisson-Boltzmann surface area analysis were performed to investigate the binding of six cisplatin derivatives with DNA. The binding affinity and potential interactions of these drugs with double-strand DNA were analyzed. The stability effect of these drugs was investigated via root-mean-square deviation and root-mean-square fluctuation analysis, which showed that some analogs can break base-pair interaction at the end of DNA and reduced the stability of DNA. Also, the results revealed that the hydrogen bond is one of the most important factors in the binding of cisplatin's adduct to DNA. Molecular mechanics Poisson-Boltzmann surface area analysis indicated that electrostatic and van der Waals interactions are the most important deriving forces to the binding of cisplatin's drug to DNA. Finally, data revealed that cisplatin and the cis-dichloro-dimethylamine-platin tendency for binding to DNA are greater than that of other analogs.
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Aminas/química , Antineoplásicos/química , Cisplatino/química , DNA/química , Antineoplásicos/farmacologia , Cisplatino/análogos & derivados , Cisplatino/farmacologia , Humanos , Ligação de Hidrogênio , Ligantes , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Reprodutibilidade dos Testes , Relação Estrutura-AtividadeRESUMO
Protein coating is a strategy for modifying and improving the surface functional properties of nanomaterials. However, the underlying mechanism behind protein coating formation, which is essential for its practical applications, remains largely unknown. Herein, we investigate the fundamental molecular mechanism of protein coating formation. Polydopamine nanospheres (PDANS) coated with bovine serum albumin (BSA) are examined in this study due to their wide biomedical potential. Our results demonstrate that BSAs can flexibly bind to PDANS and maintain their structural dynamicity. Our findings unveil that regular structure formation arises from BSAs lateral interactions via electrostatic forces. Notably, the protein coating modified PDANS surface enhances cell adhesion and proliferation as well as osteogenic differentiation. Such an enhancement is attributed to complementary surface properties provided by the dynamic PDANS-BSA complex and regular structure caused by BSA-BSA interactions in protein coating formation. This study provides a fundamental understanding of the molecular mechanism of protein coating formation, which facilitates the further development of functional protein-coated nanomaterials and guides the bioengineering decision making for biomedical applications, especially in bone tissue engineering.
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Nanosferas , Soroalbumina Bovina , Diferenciação Celular , Indóis , Osteogênese , PolímerosRESUMO
After synthesizing and identifying the nature of the new complex based on platinum metal, [Pt(NH3)2(butylgly)]NO3, the interaction of this complex with human serum albumin (HSA) was performed by spectroscopy and molecular docking methods at two temperatures of 27 and 37 °C and under physiological conditions of the body. The toxicity test of this complex was performed on the MCF-7 cell line (IC50 = 300 µM). Enthalpy, entropy, Gibbs free energy, binding constant, number of complex binding sites on the HSA, Scatchard diagrams, Hill coefficient, and Hill constant were calculated and then plotted via UV/Vis. According to the Gibbs free energy obtained at two temperatures of 27 and 37 °C (-20.6, -21.2 kJ mol-1), the interaction was done spontaneously. Moreover, the melting temperature of human serum albumin with this complex; and the kinetics of this interaction (the second-order) were calculated. Using fluorescence at three temperatures of 25, 27, and 37 °C, the binding constant (2.9 × 104, 1.0 × 104, and 5.7 × 103 M-1), the quenching constant, average aggregation number of HSA, and the number of binding sites of the complex on the protein were obtained. As well, the static quenching mechanism was also observed. Molecular docking results showed that the site of binding of this complex to the HSA, is the site II subdomain IIIA, and the hydrogen and hydrophobic bonds are superior.
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Antineoplásicos/farmacologia , Simulação de Acoplamento Molecular , Compostos Organoplatínicos/farmacologia , Albumina Sérica Humana/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Estrutura Molecular , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Espectrometria de Fluorescência , Espectrofotometria UltravioletaRESUMO
In the present study, the simultaneous carrier ability of natural antioxidant of astaxanthin (ATX) and chemotherapeutic drug of 5-fluorouracil (5-FU) by whey protein of ß-lactoglobulin (ß-LG) using various spectroscopic techniques (UV-visible, fluorescence, circular dichroism (CD) and dynamic light scattering) in combination with molecular docking were investigated (at room and physiological temperatures). According to the fluorescence quenching tests, the binding parameters between drug and ATX with protein showed that the number of their binding sites was the same in the single and competitive states. Molecular docking results have showed completely consistent with the fluorescence data that presented the independent binding sites for 5-FU and ATX on ß-LG. Also, analysis of Far-UV-CD showed that the simultaneous binding of the drugs to the protein partially enhances its stability, which is associated with the decreasing in ß-sheet structure and increasing in α-helix. According to the Zeta potential measurements in the presence of different concentrations of the drugs, they have stronger binding to the protein at lower concentrations. Therefore, given the remarkable features of ß-LG, including the ability to interact simultaneously with the natural compound of ATX and the antitumor drug of 5-FU, this study could provide useful information for the development and improvement of new protein carrier systems with synergism potency. Communicated by Ramaswamy H. Sarma.
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Lactoglobulinas , Preparações Farmacêuticas , Antioxidantes , Sítios de Ligação , Dicroísmo Circular , Fluoruracila/farmacologia , Lactoglobulinas/metabolismo , Simulação de Acoplamento Molecular , Ligação Proteica , Espectrometria de Fluorescência , Termodinâmica , Proteínas do Soro do Leite , XantofilasRESUMO
Previous reports have shown that protein-drug interaction helps to improve the pharmacokinetics of the drugs. Human serum albumin (HSA) is one of the basic components of blood plasma and it serves as a storage and carrier protein. In the present study, the interaction of a new synthesized Pt [iso]2 complex (cis - [Pt(NH2-Isopentylamine)2(Isopentylglycine)]NO3) with HSA was studied using the spectroscopic methods of fluorescence and circular dichroic (CD) at two different temperatures of 25 and 37 °C. Analysis of the quenching mechanism via Stern-Volmer curve, determination of HSA binding parameters (0.65 × 104 and 2.27 × 104) and standard Gibbs free energy (-25.8, and 21.77) at 25 and 37 °C, respectively, carried out using fluorescence quenching data. Data analysis showed that the static mechanism has the main role in fluorescence quenching. Also, the number of protein binding sites for complex indicated one binding site at two temperatures of 25 and 37 °C. The secondary structure of protein in the presence of different concentrations of Pt(II) complex did not show any significant alterations. Whereas, thermal stability of the HSA was reduced in the presence of complex. Also, thermal analysis obtained the values of ΔG°25 for HSA and HSA in presence of Pt [Iso]2 20, 13, respectively. According to the above results, we concluded that the new synthesized Pt complex can bind to the blood carrier protein of HSA and change the stability of it which can be considered in the design of new drugs.Communicated by Ramaswamy H. Sarma.
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Proteínas de Transporte , Compostos de Platina/farmacologia , Albumina Sérica , Sítios de Ligação , Dicroísmo Circular , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Espectrometria de Fluorescência , TermodinâmicaRESUMO
Cellulose nanocrystals (CNCs) are known as nano-biomaterials that can be achieved from the different sources. The designated CNCs have been successfully fabricated from the roots of Dorema kopetdaghens (Dk) plant by sulphuric acid hydrolysis method. Structural analysis has been carried out by the means of XRD, FTIR, and TGA/DTG procedures. The XRD results have indicated that the crystalline structure of CNCs had been cellulose I with the crystallinity index of 83.20% and size of 4.95 nm. The FTIR spectra have shown that the resulting samples have been related to the cellulose species. The thermal properties of CNCs have exhibited a lower thermal stability in comparison to the untreated roots. It has been indicated by the morphological analyses of FESEM, TEM, and AFM that the nanoparticles had contained a spherical shape. Also, the cytotoxicity of CNCs against A549 cell line has not exhibited any cytotoxic effects. The analysis of labeling efficiency in regards to 99mTc-CNCs has been observed to be above 98%, while the biodistribution of radioactivity has displayed a high uptake by the kidneys and blood circulation. Therefore, it is possible to transform the low-cost by-product into a beneficial substance such as CNCs that can be utilized in bioimaging applications.
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Celulose , Nanopartículas , Raízes de Plantas/química , Tecnécio , Células A549 , Animais , Celulose/química , Celulose/farmacocinética , Celulose/farmacologia , Humanos , Masculino , Nanopartículas/química , Nanopartículas/uso terapêutico , Ratos , Ratos Wistar , Tecnécio/química , Tecnécio/farmacocinética , Tecnécio/farmacologia , Distribuição TecidualRESUMO
Communicated by Ramaswamy H. Sarma.
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Antineoplásicos/farmacologia , Catalase/química , Catalase/metabolismo , Fígado/enzimologia , Oxaliplatina/farmacologia , Animais , Antineoplásicos/química , Bovinos , Dicroísmo Circular , Cinética , Simulação de Acoplamento Molecular , Oxaliplatina/química , Espectrometria de Fluorescência , Relação Estrutura-Atividade , TemperaturaRESUMO
Considering the importance of pharmacology and the influence of drugs on biological materials, the effects of a newly designed and synthesized platin complex (2,2'-Bipyridine-3,3'-dicarboxylic acid, oxalato Platinum(II), as an antitumor drug was tested on the structure of blood carrier protein of human serum albumin (HSA) using various spectroscopic techniques including UV-visible, fluorescence, and circular dichroism at 25 and 37 °C. Results of the fluorescence measurements revealed that adding the complex caused reduction in intrinsic fluorescence emission of HSA resulted from dynamic quenching of HSA. The number of binding sites and binding constants were calculated at both temperatures of 25 and 37 °C. In addition, in order to identify the complex's binding site on HSA employing spectroscopy, the competitive studies were followed using warfarin, digitoxin and ibuprofen as site markers of Sudlow sites I, II and III. Competitive binding test results have shown that Pt(II) complex bind on the warfarin binding site (or Sudlow sites I) on HSA. Besides, a reduction in thermal stability for HSA was observed in the presence of the newly designed Pt(II) complex.