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1.
Anal Chem ; 96(2): 668-675, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38176010

RESUMO

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.


Assuntos
Chumbo , Longevidade , Animais , Camundongos , Chumbo/toxicidade , Camundongos Endogâmicos C57BL , Leucócitos , Eritrócitos
2.
J Mater Sci Mater Med ; 35(1): 4, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38206473

RESUMO

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.


Assuntos
Neoplasias Colorretais , Nanopartículas , Oxalidaceae , Humanos , Ligação Proteica , Paládio , Apoptose , Neoplasias Colorretais/tratamento farmacológico
3.
J Fluoresc ; 29(4): 827-835, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31218597

RESUMO

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.


Assuntos
Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/metabolismo , Albumina Sérica Humana/metabolismo , Ligação Competitiva , Humanos , Ligação Proteica , Espectrometria de Fluorescência
4.
J Fluoresc ; 28(2): 551-559, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29476398

RESUMO

In the present study, the biological activities of a new synthesized Pt(II)-complex, 2,2' bipyridinphenyl isopentylglycin Pt(II) nitrate was investigated via its interaction with the most important blood carrier protein of human serum albumin (HSA), using fluorescence and Far-UV circular dichroism (CD) spectroscopic techniques and also molecular docking. Moreover, cytotoxicity activity of the complex was studied against breast cancer cell line of MDA MB231 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The Pt(II)-complex has a strong ability to quench the intrinsic fluorescence of HSA through a static quenching mechanism. According fluorescence quenching data, the binding parameters of the interaction were calculated and showed that hydrophobic interaction has an important role. The molecular docking results in coherent with fluorescence measurements illustrated that Pt(II) complex can bind to HSA at one position that located in the hydrophobic cavity of groove between drug site I and II. Also, experimental data on driving force in binding site was confirmed whereas theoretical results demonstrated Pt(II) complexinteract to HSA by hydrophobic interaction. Far-UV-CD results showed that Pt(II)-complex induced an increasing in the content of α-helical structure of the protein and stabilized it. Also, MTT assay represented growth inhibitory effect of the complex toward the breast cancer cell line.


Assuntos
Neoplasias da Mama/patologia , Simulação de Acoplamento Molecular , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/farmacologia , Piridinas/química , Albumina Sérica Humana/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sítios de Ligação , Humanos , Células MCF-7 , Compostos Organoplatínicos/química , Compostos Organoplatínicos/metabolismo , Ligação Proteica , Conformação Proteica , Albumina Sérica Humana/química , Análise Espectral , Termodinâmica
5.
J Biol Inorg Chem ; 22(7): 1055-1064, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28779308

RESUMO

The aim of this work is the identification of the structural effect of amino acid-Pd complex on DNA as an intracellular target which was studied using various spectroscopic techniques such as fluorescence, UV-visible and circular dichroism in combination with a molecular docking study. Hence, a novel water-soluble palladium complex, [Pd(phendione)(isopentylglycine)]NO3, has been synthesized and characterized by spectroscopic method. The anticancer activity of complex was investigated against human colon cancer cell line of HCT116 after 24 h of incubation using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. In addition, this complex was interacted with calf thymus DNA (ct-DNA) via positive cooperative interaction. The fluorescence data indicate that Pd complex is intercalated in DNA. These results were confirmed by circular dichroism spectra. The molecular docking results indicate that docking may be an appropriate method for the prediction and confirmation of experimental results. Complementary molecular docking results may be useful for the determination of the binding mechanism of DNA in pharmaceutical and biophysical studies providing new insight into the novel pharmacology and new solutions in the formulation of advanced oral drug delivery systems. Docking and spectroscopic studies show that new water-soluble Pd complex has anticancer activity and it can bind to DNA via intercalation and groove binding.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Complexos de Coordenação/farmacologia , Glicina/farmacologia , Substâncias Intercalantes/farmacologia , Paládio/farmacologia , Animais , Antineoplásicos/química , Bovinos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Complexos de Coordenação/química , DNA/metabolismo , Glicina/análogos & derivados , Humanos , Substâncias Intercalantes/química , Simulação de Acoplamento Molecular , Paládio/química
6.
J Fluoresc ; 27(5): 1829-1838, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28555407

RESUMO

In the present study, biological evaluation of a new synthesized anti-cancer compound, amyl-glycine1, 10-phenanthroline Platinum nitrate (Pt(II) complex), was investigated at different temperatures by spectroscopic methods (far-UV circular dichroism (CD) and fluorescence) and modeling methods (docking and FRET). Human serum albumin (HSA), one of the vital proteins in drug delivery system in the body, was used as a target protein. The Pt(II) complex is able to quench the intrinsic fluorescence of HSA considerably. Binding and thermodynamic parameters of the interaction between the protein and the ligand were analyzed by fluorescence quenching method. The far-UV CD spectra revealed that the secondary structure of HSA did not show any noticeable change upon interaction with Pt(II) complex at both 25 and 37°C. The calculation of fluorescence resonance energy transfer (FRET) confirmed that quenching mechanism is static, and the observed distance between the donor and acceptor is 1.18 nm. Molecular docking results are in agreement with experimental data suggesting that there is one site on HSA at which Pt(II) complex binds spontaneously. Moreover, docking results together with FRET evaluation illustrated that Pt(II) complex is located near Trp214 at a distance of 1.96 nm. Our experimental and theoretical results indicated that the driving forces for Pt(II) complex interaction with HSA are hydrogen bonding and van der Waals interactions. The combination of molecular docking and spectroscopy methods suggested that use of this new Pt(II) complex as an anti-cancer agent, is an effective innovative approach in cancer chemotherapy providing a better understanding of effects of new designed drugs.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Glicina/análogos & derivados , Glicina/farmacologia , Modelos Moleculares , Fenantrolinas/farmacologia , Albumina Sérica Humana/química , Antineoplásicos/química , Sítios de Ligação , Complexos de Coordenação/química , Glicina/química , Humanos , Simulação de Acoplamento Molecular , Fenantrolinas/química , Ligação Proteica , Conformação Proteica , Albumina Sérica Humana/metabolismo , Espectrometria de Fluorescência , Termodinâmica
7.
Nanomedicine ; 13(5): 1685-1692, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28343017

RESUMO

Thanks to the progress of nanotechnology there are several agent-delivery systems that can be selected to achieve rapid and specific delivery of a wide variety of biologically active agents. Consequently, the manipulation and engineering of biopolymers has become one of the most exciting subjects for those who study delivery systems on the nanoscale. In this regard, both nanoparticle formation and a carrier role have been observed in the case of the globular milk whey protein, ß-lactoglobulin (ß-LG), setting it apart from many other proteins. To date, many efforts adopting different approaches have created ß-LG nanoparticles useful in forming delivery systems for various agents with specific targets. In this review, the potential of ß-LG to play the role of an efficient and diverse carrier protein, as well as its ability to form a well-targeted nano-scale delivery system is discussed.


Assuntos
Sistemas de Liberação de Medicamentos , Lactoglobulinas , Nanopartículas , Animais , Humanos , Leite , Proteínas do Leite , Proteínas do Soro do Leite
8.
Acta Chim Slov ; 61(1): 126-36, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24664336

RESUMO

A new anionic 8-hydroxyquinolinatopalladate(II) complex with malonate has been synthesized and characterized by elemental analysis, conductivity, FT-IR, UV-Vis and 1H NMR techniques to enhance the development of potential anticancer agents. Cytotoxicity was determined against the human leukemia cells, molt, by MTT assay. The novel antitumor Pd(II) complex was evaluated for its binding to calf thymus DNA (ctDNA) in physiological buffer (pH 7.0) by using absorption spectroscopy, fluorescence titration spectra, ethidium bromide displacement and gel chromatography studies. The results obtained from these analyses indicated that the water-soluble complex can bind to DNA cooperatively through a static quenching procedure at low concentrations. Thermodynamic parameters obtained from fluorescence experiments at different temperatures revealed the hydrogen binding and van der Waals force in the binding process which was supported by Scatchard's plots.


Assuntos
Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , DNA/metabolismo , Compostos Organometálicos/metabolismo , Compostos Organometálicos/farmacologia , Paládio/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Técnicas de Química Sintética , Humanos , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Termodinâmica
9.
J Gastrointest Cancer ; 55(2): 599-624, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38411875

RESUMO

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.


Assuntos
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 , Multiômica
10.
Int J Biol Macromol ; 266(Pt 2): 131298, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574913

RESUMO

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.


Assuntos
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/química
11.
J Pharm Sci ; 112(4): 1072-1080, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36503002

RESUMO

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.


Assuntos
Quitosana , Sistemas de Liberação de Medicamentos , Cápsulas/química , Microscopia Eletrônica de Transmissão , Quitosana/química , Polímeros/química , Portadores de Fármacos/química
12.
Heliyon ; 9(5): e15911, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37223709

RESUMO

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.

13.
J Biomol Struct Dyn ; : 1-13, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37937794

RESUMO

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.

14.
J Dairy Res ; 79(2): 209-15, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22559063

RESUMO

The effect of copper(II) ions (Cu(+2)) on the structure of ß-lactoglobulin (ß-lg) was investigated spectroscopically using UV-visible, fluorescence and circular dichroism (CD) and calorimetrically using isothermal titration calorimetry (ITC), at different temperatures. Results of the UV-visible studies showed that adding Cu(+2) to ß-lg solution caused increasing turbidity, indicative of protein aggregation. It was noticeable that the rate of increasing turbidity was directly proportional to increasing temperature. The far-UV CD studies displayed that the Cu(+2) cannot induce any significant changes in the secondary structures of ß-lg at different temperatures. Also, the ITC data indicated that the binding process of Cu(+2) to ß-lg is mainly entropically driven. The results highlight that copper ions cause the tertiary structure of ß-lg to change and induce a slightly open structure leading to the formation of supramolecular aggregates in ß-lg which may result in the reduced allergenicity of ß-lg and its increased use in industrial applications.


Assuntos
Cobre/química , Lactoglobulinas/química , Calorimetria , Cátions Bivalentes , Dicroísmo Circular , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Termodinâmica
15.
Eur J Pharm Biopharm ; 172: 168-176, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35149192

RESUMO

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.


Assuntos
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 , Ratos
16.
Food Sci Nutr ; 10(11): 3585-3597, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36348777

RESUMO

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.

17.
Phenomics ; 2(1): 18-32, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36939771

RESUMO

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.

18.
Food Chem ; 367: 130617, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34352696

RESUMO

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.


Assuntos
Nanopartículas Metálicas , Prata , DNA/genética , Glicina/análogos & derivados , Humanos , Glifosato
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 267(Pt 2): 120538, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34749259

RESUMO

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.


Assuntos
Caseínas , Nanopartículas , Sítios de Ligação , Dicroísmo Circular , Fluoruracila , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Espectrometria de Fluorescência , Termodinâmica
20.
Acta Chim Slov ; 58(4): 811-22, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24061133

RESUMO

In this study two platinum(II) and palladium(II) complexes of the type [M(bpy)(pip-dtc)]NO3 (where M=Pt(II) or Pd(II), bpy=2,2'-bipyridine, pip-dtc=piperidinedithiocarbamate) were synthesized by reaction between diaquo-2,2'-bipyridine Pt(II)/Pd(II) nitrate and sodium salt of dithiocarbamate. These cationic water soluble complexes were characterized by elemental analysis, molar conductance, IR, electronic and 1H NMR spectroscopic studies. The cyclic dithiocarbamate was found to coordinate as bidentate fasion with Pt(II) or Pd(II) center. Their biological activities were tested against chronic myelogenous leukemia cell line, K562, at micromolar concentration. The obtained cytotoxic concentration (IC50) values were much lower than cisplatin. The interaction of these complexes with highly polymerized calf thymus DNA (ct-DNA) was extensively studied by means of electronic absorption, fluorescence, circular dichroism and other measurements. The experimental results, thermodynamic and binding parameters, suggested that these complexes cooperatively bind to DNA presumably via intercalation. Moreover, the tendency of the Pt(II) complex to interact with DNA was more than that of Pd(II) complex.

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