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1.
Mol Pharm ; 18(2): 550-575, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-32519875

RESUMEN

The poor healing associated with chronic wounds affects millions of people worldwide through high mortality rates and associated costs. Chronic wounds present three main problems: First, the absence of a suitable environment to facilitate cell migration, proliferation, and angiogenesis; second, bacterial infection; and third, unbalanced and prolonged inflammation. Unfortunately, current therapeutic approaches have not been able to overcome these main issues and, therefore, have limited clinical success. Over the past decade, incorporating the unique advantages of nanomedicine into wound healing approaches has yielded promising outcomes. Nanomedicine is capable of stimulating various cellular and molecular mechanisms involved in the wound microenvironment via antibacterial, anti-inflammatory, and angiogenetic effects, potentially reversing the wound microenvironment from nonhealing to healing. This review briefly discusses wound healing mechanisms and pathophysiology and then highlights recent findings regarding the opportunities and challenges of using nanomedicine in chronic wound management.


Asunto(s)
Portadores de Fármacos/química , Nanopartículas/química , Piel/lesiones , Nanomedicina Teranóstica/métodos , Cicatrización de Heridas/efectos de los fármacos , Actinobacteria , Inductores de la Angiogénesis/administración & dosificación , Inductores de la Angiogénesis/farmacocinética , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacocinética , Vendajes , Enfermedad Crónica/tratamiento farmacológico , Modelos Animales de Enfermedad , Composición de Medicamentos/métodos , Humanos , Hidrogeles/química , Nanopartículas/administración & dosificación , Neovascularización Fisiológica/efectos de los fármacos , Fármacos Fotosensibilizantes/administración & dosificación , Terapia Fototérmica/métodos , Piel/efectos de los fármacos , Piel/inmunología , Piel/microbiología , Cicatrización de Heridas/fisiología
2.
Chem Rev ; 119(21): 11352-11390, 2019 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-31490059

RESUMEN

The adult myocardium has a limited regenerative capacity following heart injury, and the lost cells are primarily replaced by fibrotic scar tissue. Suboptimal efficiency of current clinical therapies to resurrect the infarcted heart results in injured heart enlargement and remodeling to maintain its physiological functions. These remodeling processes ultimately leads to ischemic cardiomyopathy and heart failure (HF). Recent therapeutic approaches (e.g., regenerative and nanomedicine) have shown promise to prevent HF postmyocardial infarction in animal models. However, these preclinical, clinical, and technological advancements have yet to yield substantial enhancements in the survival rate and quality of life of patients with severe ischemic injuries. This could be attributed largely to the considerable gap in knowledge between clinicians and nanobioengineers. Development of highly effective cardiac regenerative therapies requires connecting and coordinating multiple fields, including cardiology, cellular and molecular biology, biochemistry and chemistry, and mechanical and materials sciences, among others. This review is particularly intended to bridge the knowledge gap between cardiologists and regenerative nanomedicine experts. Establishing this multidisciplinary knowledge base may help pave the way for developing novel, safer, and more effective approaches that will enable the medical community to reduce morbidity and mortality in HF patients.


Asunto(s)
Insuficiencia Cardíaca/terapia , Nanomedicina/métodos , Medicina Regenerativa/métodos , Animales , Insuficiencia Cardíaca/prevención & control , Humanos
3.
Eur J Nutr ; 59(7): 3149-3161, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31802196

RESUMEN

PURPOSE: There is a direct association between salt intake and blood pressure (BP), one of the main risk factors for CVDs. However, yet there has been a debate that how strong is this association in people with and without hypertension. This study was conducted to evaluate the magnitude of the association between salt intake and BP in hypertensive and normotensive population among a nationally representative population. METHODS: The study was conducted on a nationally representative sample of 18,635 Iranian adults aged 25 years and older who participated in the STEPS survey 2016 and provided urine sample. Salt intake was estimated through spot urine sample and Tanaka equation. Multiple linear regression model in survey data analysis was used to assess the independent effect of salt intake on BP. RESULTS: After adjusting for covariates, there was a significant association between salt intake and SBP in hypertensive (p < 0.001) and normotensive people (p < 0.001). In hypertensive people, with 1 g of increase in salt intake, the SBP and DBP increased 0.37 mmHg and 0.07 mmHg, respectively. Whereas in normotensive people, with 1 g of increase in salt intake, the SBP and DBP increased 0.26 mmHg and 0.05 mmHg, respectively. Moreover, there was a significant trend toward an increase of SBP across salt intake quartiles in both hypertensive (p < 0.001) and normotensive people (p = 0.002), though the slope was steeper in hypertensive than in normotensive people. CONCLUSIONS: The present study demonstrated that salt intake significantly increased SBP in both hypertensive and normotensive people, though the magnitude of this increase was greater in hypertensive people as compared with normotensive people.


Asunto(s)
Presión Sanguínea/efectos de los fármacos , Encuestas Epidemiológicas , Hipertensión/dietoterapia , Cloruro de Sodio Dietético/administración & dosificación , Cloruro de Sodio Dietético/farmacología , Adulto , Conducta Alimentaria , Femenino , Humanos , Irán , Masculino , Persona de Mediana Edad , Cloruro de Sodio Dietético/orina
4.
Nanoscale ; 15(43): 17342-17349, 2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-37860936

RESUMEN

The biological behavior and fate of nanoparticles are dependent on their retention time in the blood circulation system. The protein corona components, especially opsonins, and dysopsonins, adsorbed on the nanoparticle surface determine their blood circulation time. The protein corona formation is a dynamic process that involves the competition between different proteins to be adsorbed on the nanoparticles. Therefore, studying how proteins compete and are oriented on the nanoparticle surface is essential. We hypothesized that the presence of opsonins (immunoglobulin (IgG)) might affect the adsorption of dysopsonins (human serum albumin (HSA)) and vice versa. Using the molecular dynamics simulations, we showed that the adsorption of HSA on the GO surface after the IgG adsorption is more probable than the opposite order of adsorption. It was also observed that the higher lateral diffusion of the HSA compared to the IgG helped the system reach a more stable configuration while the initial adsorption of the HSA limits the lateral diffusion of IgG. Therefore, replacing IgG adsorbed on the GO surface with HSA is plausible while the reverse process is less likely to occur. This study revealed that albumin might extend the blood circulation time of GO by replacing opsonins (IgG).


Asunto(s)
Nanopartículas , Corona de Proteínas , Humanos , Proteínas Opsoninas , Nanopartículas/metabolismo , Albúmina Sérica Humana , Inmunoglobulina G , Adsorción
5.
ACS Nano ; 17(13): 12458-12470, 2023 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-37379064

RESUMEN

The therapeutic efficacy and adverse impacts of nanoparticles (NPs) are strongly dependent on their systemic circulation time. The corona proteins adsorbed on the NPs determine their plasma half-lives, and hence, it is crucial to identify the proteins shortening or extending their circulation time. In this work, the in vivo circulation time and corona composition of superparamagnetic iron oxide nanoparticles (SPIONs) with different surface charges/chemistries were analyzed over time. SPIONs with neutral and positive charges showed the longest and shortest circulation times, respectively. The most striking observation was that corona-coated NPs with similar opsonin/dysopsonin content showed different circulation times, implying these biomolecules are not the only contributing factors. Long-circulating NPs adsorb higher concentrations of osteopontin, lipoprotein lipase, coagulation factor VII, matrix Gla protein, secreted phosphoprotein 24, alpha-2-HS-glycoprotein, and apolipoprotein C-I, while short-circulating NPs adsorb higher amounts of hemoglobin. Therefore, these proteins may be considered to be determining factors governing the NP systemic circulation time.


Asunto(s)
Nanopartículas , Corona de Proteínas , Tiempo de Circulación Sanguínea , Corona de Proteínas/metabolismo , Nanopartículas Magnéticas de Óxido de Hierro , Proteínas Sanguíneas
6.
Theranostics ; 13(8): 2710-2720, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37215574

RESUMEN

Rationale: Efficient labeling methods for mesenchymal stem cells (MSCs) are crucial for tracking and understanding their behavior in regenerative medicine applications, particularly in cartilage defects. MegaPro nanoparticles have emerged as a potential alternative to ferumoxytol nanoparticles for this purpose. Methods: In this study, we employed mechanoporation to develop an efficient labeling method for MSCs using MegaPro nanoparticles and compared their effectiveness with ferumoxytol nanoparticles in tracking MSCs and chondrogenic pellets. Pig MSCs were labeled with both nanoparticles using a custom-made microfluidic device, and their characteristics were analyzed using various imaging and spectroscopy techniques. The viability and differentiation capacity of labeled MSCs were also assessed. Labeled MSCs and chondrogenic pellets were implanted into pig knee joints and monitored using MRI and histological analysis. Results: MegaPro-labeled MSCs demonstrated shorter T2 relaxation times, higher iron content, and greater nanoparticle uptake compared to ferumoxytol-labeled MSCs, without significantly affecting their viability and differentiation capacity. Post-implantation, MegaPro-labeled MSCs and chondrogenic pellets displayed a strong hypointense signal on MRI with considerably shorter T2* relaxation times compared to adjacent cartilage. The hypointense signal of both MegaPro- and ferumoxytol-labeled chondrogenic pellets decreased over time. Histological evaluations showed regenerated defect areas and proteoglycan formation with no significant differences between the labeled groups. Conclusion: Our study demonstrates that mechanoporation with MegaPro nanoparticles enables efficient MSC labeling without affecting viability or differentiation. MegaPro-labeled cells show enhanced MRI tracking compared to ferumoxytol-labeled cells, emphasizing their potential in clinical stem cell therapies for cartilage defects.


Asunto(s)
Enfermedades de los Cartílagos , Trasplante de Células Madre Mesenquimatosas , Nanopartículas , Animales , Porcinos , Óxido Ferrosoférrico , Células Madre , Cartílago , Imagen por Resonancia Magnética/métodos , Diferenciación Celular , Trasplante de Células Madre Mesenquimatosas/métodos , Rastreo Celular/métodos
7.
Neurotoxicology ; 85: 145-159, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34058247

RESUMEN

The amyloid-beta (Aß) fibrillation process seems to execute a principal role in the neuropathology of Alzheimer's disease (AD). Accordingly, novel therapeutic plans have concentrated on the inhibition or degradation of Aß oligomers and fibrils. Biocompatible nanoparticles (NPs), e.g., gold and iron oxide NPs, take a unique capacity in redirecting Aß fibrillation kinetics; nevertheless, their impacts on AD-related memory impairment have not been adequately evaluated in vivo. Here, we examined the effect of commercial PEGylated superparamagnetic iron oxide nanoparticles (SPIONs) on the learning and memory of an AD-animal model. The outcomes demonstrated the dose-dependent effect of SPIONs on Aß fibrillation and learning and memory processes. In vitro and in vivo findings revealed that Low doses of SPIONs inhibited Aß aggregation and ameliorated learning and memory deficit in the AD model, respectively. Enhanced level of hippocampal proteins, including brain-derived neurotrophic factor, BDNF, phosphorylated-cAMP response element-binding protein, p-CREB, and stromal interaction molecules, e.g., STIM1 and STIM2, were also observed. However, at high doses, SPIONs did not improve the detrimental impacts of Aß fibrillation on spatial memory and hippocampal proteins expression. Overall, we revealed the potential capacity of SPIONs on retrieval of behavioral and molecular manifestations of AD in vivo, which needs further investigations to determine the mechanistic effect of SPIONs in the AD conundrum.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Aprendizaje/efectos de los fármacos , Nanopartículas Magnéticas de Óxido de Hierro/administración & dosificación , Trastornos de la Memoria/tratamiento farmacológico , Polietilenglicoles/administración & dosificación , Moléculas de Interacción Estromal , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/toxicidad , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Reacción de Fuga/efectos de los fármacos , Reacción de Fuga/fisiología , Aprendizaje/fisiología , Masculino , Trastornos de la Memoria/metabolismo , Fragmentos de Péptidos/toxicidad , Ratas , Ratas Wistar , Molécula de Interacción Estromal 1/metabolismo , Molécula de Interacción Estromal 2/metabolismo , Moléculas de Interacción Estromal/metabolismo
8.
Environ Sci Pollut Res Int ; 28(13): 16744-16753, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33398731

RESUMEN

Cancer is the second leading cause of death in the world and the third leading cause of death in Iran. It has been proven that numerous cancer cases are caused by exposure to environmental pollutants. There is a public health concern regarding an increase in exposure to carcinogens across Iran through different sources (air, food, and water) and a lack of research to address this issue. This study aims to gather data on exposure to heavy metals, polycyclic aromatic hydrocarbons (PAHs), and pesticides and their intake routes during the implementation of a national population health survey. This is a cross-sectional study of environmental pollutants in Iran, with a stratified multi-stage random sampling method, which led to 660 nationally representative samples in 132 clusters in three sequential parts. The first will be questionnaires to obtain demographics, assets, food records, air quality, and food frequency. The second will be physical measurements, including anthropometric and body composition. The third will be lab assessments that measure 26 types of environmental pollutants (7 heavy metals, 16 PAHs, and 3 pesticides) in urine, inhaled air, and consumed food and water of the population under study using ICP-MS and GS-MS devices. The results of this study will inform policymakers and the general population regarding the level of threat and will provide evidence for the development of interventional and observatory plans on the reduction of exposures to these pollutants. It could also be used to develop local standards to control contaminants through the three exposure routes. This study protocol will obtain data needed for policymakers to set surveillance systems for these pollutants at the national and provincial level to address the public concerns regarding the contamination of food, air, and water.


Asunto(s)
Metales Pesados , Plaguicidas , Hidrocarburos Policíclicos Aromáticos , Salud Poblacional , Estudios Transversales , Monitoreo del Ambiente , Humanos , Irán , Metales Pesados/análisis , Plaguicidas/análisis , Hidrocarburos Policíclicos Aromáticos/análisis
9.
PLoS One ; 16(3): e0241926, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33657130

RESUMEN

INTRODUCTION: To integrate and execute a proper preventive plan and reduce the risk of non-communicable diseases (NCDs), policy makers need to have access to both reliable data and a unique definition of metabolic syndrome (MetS). This study was conducted on the data collected by cross-sectional studies of WHO's STEPwise approach to surveillance of NCD risk factors (STEPs) to estimate the national and sub-national prevalence rates of MetS in Iran in 2016. MATERIALS AND METHODS: The prevalence of MetS was estimated among 18,414 individuals aged ≥25 years living in urban and rural areas of Iran using various definition criteria; National Cholesterol Education Program Adult Treatment Panel III 2004 (ATP III), International Diabetes Federation (IDF), American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI), Joint Interim Statement (JIS). Regional IDF (RIDF) and JIS (RJIS) were defined using ethnicity-specific values of waist circumference for the country. RESULTS: National prevalence rate of MetS based on ATP III, IDF, AHA/NHLBI, JIS, RIDF and RJIS criteria were 38.3% (95% CI 37.4-39.1), 43.5% (42.7-44.4), 40.9% (40.1-41.8), 47.6% (46.8-48.5), 32.0% (31.2-32.9), and 40.8% (40.0-41.7), respectively. The prevalence was higher among females, in urban residents, and those aged 65-69 years. MetS was expected to affect about 18.7, 21.3, 20.0, 23.3, 15.7, and 20.0 million Iranians, respectively, based on ATP III, IDF, AHA/NHLBI, JIS, RIDF and RJIS. The two most common components noted in this population were reduced high-density lipoprotein cholesterol (HDL-C) levels and central obesity. CONCLUSION: High prevalence rate of MetS among Iranian adults is alarming, especially among females, urban residents, and the elderly. The JIS definition criteria is more appropriate to determine higher number of Iranians at risk of NCDs. Proper management and prevention of MetS is required to adopt multiple national plans including lifestyle modifications, medical interventions, and public education on NCDs risk factors.


Asunto(s)
Síndrome Metabólico/epidemiología , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Irán/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo
10.
Arch Iran Med ; 24(1): 48-57, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33588568

RESUMEN

BACKGROUND: Non-communicable diseases (NCDs) are one of the greatest threats to public health, and have been related to poor quality dietary patterns. This study was conducted to determine the distribution of dietary risk factors in Iran. METHODS: Cross-sectional data was gathered between April and November 2016 from 30,541 eligible adults (out of 31 050 individuals who were selected through systematic proportional to size cluster random sampling) living in urban and rural areas, using the WHO-based STEPs risk factor questionnaire. Low intakes of fruits, vegetables, dairy products, and fish, and high intakes of salty processed food (SPF), as well as daily intake of hydrogenated fat (HF) were considered as nutritional risk factors. RESULTS: At the national level, 82.8% (95% CI: 82.4-83.2), 57.8% (95% CI: 57.2-58.4), 80.6% (95% CI: 80.1-81) and 90.3% (95% CI: 90-90.6) of participants of all age groups had sub-optimal intakes of fruits, vegetables, dairy products and fish, respectively. Furthermore, 12.8% (95% CI: 12.4-13.1), and 29.4% (95% CI: 28.9-29.9) of respondents had high SPF intakes and HF use, respectively. At the sub-national level, the highest distribution of suboptimal intake of fruits (97.2%; 95% CI:96-98.3), vegetables (79.2%; 95% CI: 76.3-82.1) and dairy products (92.9%; 95% CI: 91-94.7) was observed in Sistan and Baluchistan. Except for Boushehr and Hormozgan, the majority of the population of other provinces consumed fish less than twice a week. Similarly, the high intake of SPF was found mostly in the population of Yazd (23.7; 95% CI: 20.2-27.2). HF consumption was the highest in North Khorasan (64.2%; 95% CI: 60.3-68.1). CONCLUSION: These findings highlight the widespread distribution of dietary risk factors in Iran, which should be a priority for the people and the politicians in order to prevent NCDs.


Asunto(s)
Dieta Saludable , Conducta Alimentaria , Estado Nutricional , Adulto , Anciano , Costo de Enfermedad , Estudios Transversales , Femenino , Humanos , Irán , Masculino , Persona de Mediana Edad , Enfermedades no Transmisibles/prevención & control , Encuestas Nutricionales , Factores de Riesgo , Adulto Joven
11.
Iran Biomed J ; 13(4): 207-13, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19946346

RESUMEN

BACKGROUND: The combustion of sulfur-rich fossil fuels leads to release of sulfur oxide pollution in the environment. In biodesulfurization process, an organism is able to remove sulfur from fossil fuels without decreasing the caloric value of those substrates. The main aim of this research was to design a recombinant microorganism to remove the highest amount of sulfur compounds in fossil fuels. METHODS: Three genes (dszA,B,C) from dsz operon are responsible for the 4S pathway (biodesulfurization pathway) in Rhodococcus erythropolis IGTS8 were inserted into the chromosome of a novel indigenous Pseudomonas putida. The reaction catalyzed by products of dszA,B,C genes require FMNH2 supplied by dszD enzyme. Thus, pVLT31 vector harboring dszD gene was transferred into this recombinant strain. RESULTS: The results demonstrated a higher biodesulfurization activity when the flavin reductase gene was transferred into recombinant P. putida harboring dszA,B,C. These results were approved by the Gibbs test and HPLC analysis. CONCLUSION: These analyses showed that this novel indigenous engineered P. putida could be a promising candidate for an industrial and environmental application for Biodesulfurization process.


Asunto(s)
Biodegradación Ambiental , Ingeniería Genética/métodos , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Compuestos de Azufre/metabolismo , Southern Blotting , Cromatografía Líquida de Alta Presión , Cromosomas Bacterianos/genética , Clonación Molecular , FMN Reductasa/genética , FMN Reductasa/metabolismo , Combustibles Fósiles , Microbiología Industrial , Óxidos/metabolismo , Oxigenasas/genética , Oxigenasas/metabolismo , Pseudomonas aeruginosa/genética , Recombinación Genética , Rhodococcus/genética
12.
Nanoscale ; 11(6): 2594-2601, 2019 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-30693921

RESUMEN

It is increasingly being accepted that bacteria are able to alter their shape/colony pattern in response to adverse environmental conditions. Morphological adaptation of bacteria is known as one of their defence mechanisms against environmental stress/variations. As nanoparticles (NPs) have a unique capacity to induce a wide range of stresses to bacteria, we hypothesized that such NPs can affect the bacterial colony pattern. To test this hypothesis, we incubated a series of superparamagnetic iron oxide nanoparticles (SPIONs) with different physicochemical properties with bacterial colonies and probed the colonies' diffraction patterns by laser. The diffraction patterns of Escherichia coli, Lactobacillus rhamnosus, and Staphylococcus aureus colonies were recorded using a laser. Our results revealed the formation of distinct bacterial diffraction patterns in response to SPIONs with various concentrations and surface chemistries. Our results may pave the way toward the development of new optical approaches for the high-throughput screening of bacterial-NPs/drugs interactions.


Asunto(s)
Bacterias/química , Nanopartículas de Magnetita/química , Fenómenos Ópticos , Propiedades de Superficie
13.
ACS Appl Mater Interfaces ; 11(50): 46408-46418, 2019 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-31729218

RESUMEN

Recent studies suggest that cancer cell death accompanied by organelle dysfunction might be a promising approach for cancer therapy. The Golgi apparatus has a key role in cell function and may initiate signaling pathways to mitigate stress and, if irreparable, start apoptosis. It has been shown that Golgi disassembly and fragmentation under oxidative stress act as indicators for stress-mediated cell death pathways through cell cycle arrest in the G2/M phase. The present study shows that UV-induced reactive oxygen species (ROS) generation by Ag@ZnO nanoparticles (NPs) transform the Golgi structures from compressed perinuclear ribbons into detached vesicle-like structures distributed in the entire cytoplasm of melanoma cells. This study also demonstrates that Ag@ZnO NP-induced Golgi fragmentation cooccurs with G2 block of cell cycle progression, preventing cells from entering the mitosis phase. Additionally, the increased intracellular ROS production triggered by Ag@ZnO NPs upon UV exposure promoted autophagy. Taken together, Ag@ZnO NPs induce stress-related Golgi fragmentation and autophagy, finally leading to melanoma cell apoptosis. Intracellular oxidative stress generated by Ag@ZnO NPs upon UV irradiation may thus represent a targeted approach to induce cancer cell death through organelle destruction in melanoma cells, while fibroblast cells remained largely unaffected.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Aparato de Golgi/efectos de los fármacos , Melanoma/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Autofagia/efectos de los fármacos , Autofagia/efectos de la radiación , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de la radiación , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Aparato de Golgi/genética , Humanos , Melanoma/genética , Melanoma/patología , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Mitosis/efectos de los fármacos , Mitosis/efectos de la radiación , Especies Reactivas de Oxígeno/química , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación , Plata/química , Plata/farmacología , Rayos Ultravioleta , Óxido de Zinc/química , Óxido de Zinc/farmacología
14.
ACS Chem Neurosci ; 10(5): 2299-2309, 2019 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-30933476

RESUMEN

Alzheimer's disease (AD) is the most common type of neurodegenerative amyloid disorder causing progressive cognitive decline and memory loss. A considerable number of therapies for AD rely on inhibition/delay/dissociation of amyloid beta (Aß) oligomers and fibrils. In this case, nanoparticles (NPs) demonstrated substantial effects on the Aß fibrillation process; however, their effects on progressive cognitive decline and memory have been poorly investigated in vivo. In this study, acquisition and retention of spatial learning and memory are studied in a rat animal model of AD after intrahippocampal (IH) and intraperitoneal (IP) injections of a model NP, i.e., gold NPs (AuNPs). The outcomes revealed that the AuNPs could improve the acquisition and retention of spatial learning and memory in Aß treated rats as indicated by decreased time (Aß: 39.60 ± 3.23 s vs Aß+AuNPs: 25.78 ± 2.80 s) and distance (Aß: 917.98 ± 50.81 cm vs Aß+AuNPs: 589.09 ± 65.96 cm) of finding the hidden platform during training days and by increased time spent in the target quadrant (Aß: 19.40 ± 0.98 s vs Aß+AuNPs: 29.36 ± 1.14 s) in the probe test in Morris water maze (MWM). Expression of brain-derived neurotrophic factor, BDNF, cAMP response element binding protein, CREB, and stromal interaction molecules, e.g., STIM1 and STIM2 was also increased, supporting improved neural survival. Our outcomes may pave a way for mechanistic insights toward the role of NPs on retrieval of the deteriorated behavioral functions in brain tissue after AD outbreak.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Oro , Nanopartículas del Metal/administración & dosificación , Molécula de Interacción Estromal 1/metabolismo , Molécula de Interacción Estromal 2/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Nanopartículas del Metal/uso terapéutico , Ratones , Fosforilación/efectos de los fármacos , Ratas , Ratas Wistar
15.
ACS Nano ; 13(3): 3243-3256, 2019 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-30810027

RESUMEN

Aggregation of the natively unfolded protein α-synuclein (α-syn) is key to the development of Parkinson's disease (PD). Some nanoparticles (NPs) can inhibit this process and in turn be used for treatment of PD. Using simulation strategies, we show here that α-syn self-assembly is electrostatically driven. Dimerization by head-to-head monomer contact is triggered by dipole-dipole interactions and subsequently stabilized by van der Waals interactions and hydrogen bonds. Therefore, we hypothesized that charged nano-objects could interfere with this process and thus prevent α-syn fibrillation. In our simulations, positively and negatively charged graphene sheets or superparamagnetic iron oxide NPs first interacted with α-syn's N/C terminally charged residues and then with hydrophobic residues in the non-amyloid-ß component (61-95) region. In the experimental setup, we demonstrated that the charged nano-objects have the capacity not only to strongly inhibit α-syn fibrillation (both nucleation and elongation) but also to disaggregate the mature fibrils. Through the α-syn fibrillation process, the charged nano-objects induced the formation of off-pathway oligomers.


Asunto(s)
Nanopartículas de Magnetita/química , Estrés Mecánico , alfa-Sinucleína/química , Dimerización , Interacciones Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Tamaño de la Partícula , Agregado de Proteínas , Propiedades de Superficie , alfa-Sinucleína/síntesis química
16.
ACS Chem Neurosci ; 10(3): 1214-1221, 2019 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-30644730

RESUMEN

Bipolar disorder is a complex neuropsychiatric disorder, characterized by intermittent episodes of mania and depression. Recent studies have indicated argyrophilic grains, composed of hyperphosphorylated tau, are observable in postmortem brains of bipolar patients. It remains uncertain how tau hyperphosphorylation results in neurodegeneration upon the disease. Recent studies have demonstrated that phosphorylated tau at Thr231 exists in two distinct cis and trans conformations, in which cis pT231-tau is highly neurotoxic and acts as an early driver of tauopathy in several neurodegenerative diseases. We herein employed an in vitro model, which resembles some aspects of bipolar disorder, to study the cis p-tau mediatory role. We established GSK3ß overexpressing SH-SY5Y cells and examined cell viability, cis p-tau formation, and lithium effects by immunofluorescence and flow cytometry. We found an increase in cis p-tau levels as well as viability decrease in the cell model. Furthermore, we discovered that lithium treatment inhibits cis p-tau formation, resulting in diminished cell death. We also examined BD and healthy human brain samples and detected cis p-tau in the patients' brains. Our results show that tauopathy, observed in bipolar disorder, is being mediated through cis p-tau and that a conformer could be the cause of neurodegeneration upon the disease. Our findings would suggest novel therapeutic target to fight the devastating disorder.


Asunto(s)
Trastorno Bipolar/metabolismo , Degeneración Nerviosa/metabolismo , Proteínas tau/metabolismo , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/patología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Compuestos de Litio/farmacología , Degeneración Nerviosa/tratamiento farmacológico , Degeneración Nerviosa/patología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Psicotrópicos/farmacología , Tauopatías/tratamiento farmacológico , Tauopatías/metabolismo , Tauopatías/patología
17.
Sci Rep ; 9(1): 1558, 2019 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-30733474

RESUMEN

Fibrinogen is one of the key proteins that participate in the protein corona composition of many types of nanoparticles (NPs), and its conformational changes are crucial for activation of immune systems. Recently, we demonstrated that the fibrinogen highly contributed in the protein corona composition at the surface of zeolite nanoparticles. Therefore, understanding the interaction of fibrinogen with zeolite nanoparticles in more details could shed light of their safe applications in medicine. Thus, we probed the molecular interactions between fibrinogen and zeolite nanoparticles using both experimental and simulation approaches. The results indicated that fibrinogen has a strong and thermodynamically favorable interaction with zeolite nanoparticles in a non-cooperative manner. Additionally, fibrinogen experienced a substantial conformational change in the presence of zeolite nanoparticles through a concentration-dependent manner. Simulation results showed that both E- and D-domain of fibrinogen are bound to the EMT zeolite NPs via strong electrostatic interactions, and undergo structural changes leading to exposing normally buried sequences. D-domain has more contribution in this interaction and the C-terminus of γ chain (γ377-394), located in D-domain, showed the highest level of exposure compared to other sequences/residues.


Asunto(s)
Fenómenos Químicos , Fibrinógeno/química , Modelos Moleculares , Nanopartículas/química , Zeolitas/química , Sitios de Unión , Humanos , Nanopartículas del Metal/química , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Nanopartículas/ultraestructura , Unión Proteica , Análisis Espectral , Termodinámica
18.
Nanoscale ; 10(3): 1228-1233, 2018 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-29292453

RESUMEN

Protein unfolding induced by nanoparticles (NPs) can lead to exposure of cryptic epitopes that might dictate biological identity and affect NP biological fate (e.g., blood circulation time, biodistribution, and tumor accumulation). Here, we monitor the conformation of fluorescence resonance energy transfer (FRET)-labelled fibronectin (FN) on corona-coated gold NPs. We found that the labelled FN proteins, which directly accessed the gold NP surface, underwent more pronounced conformational changes than those associated with the protein corona via protein-protein interactions. FRET and liquid chromatography-mass spectrometry analyses demonstrated that NP size/concentration, pH change, and the level of surface coverage by the corona can tune the accessibility of labelled FN to the gold NP surface. Although some subsequently adsorbing proteins accessed the NP surface thanks to incomplete surface coverage and protein exchange (the Vroman effect), most outer-layer proteins could not directly bind to the NP surface, blocked by pre-adsorbed corona layers. This finding was also partially confirmed by isothermal titration calorimetry (ITC) analysis. These results suggest the proof-of-concept that outermost-layer proteins with modestly changed conformation rather than unfolded proteins at the gold NP surface effectively create the NPs' biological identity, which might have important implications on biological fates of gold NPs.


Asunto(s)
Fibronectinas/química , Nanopartículas del Metal , Corona de Proteínas , Transferencia Resonante de Energía de Fluorescencia , Oro , Humanos , Conformación Proteica , Desplegamiento Proteico
19.
ACS Chem Neurosci ; 9(7): 1725-1734, 2018 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-29676567

RESUMEN

Amyloid beta (Aß), which forms toxic oligomers and fibrils in brain tissues of patients with Alzheimer's disease, is broadly used as a model protein to probe the effect of nanoparticles (NPs) on oligomerization and fibrillation processes. However, the majority of the reports in the field have ignored the effect of the biomolecular corona on the fibrillogenesis of the Aß proteins. The biomolecular corona, which is a layer composed of various types of biomolecules that covers the surface of NPs upon their interaction with biological fluids, determines the biological fates of NPs. Therefore, during in vivo interaction of NPs with Aß protein, what the Aß actually "sees" is the human plasma and/or cerebrospinal fluid (CSF) biomolecular-coated NPs rather than the pristine surface of NPs. Here, to mimic the in vivo effects of therapeutic NPs as antifibrillation agents, we probed the effects of a biomolecular corona derived from human CSF and/or plasma on Aß fibrillation. The results demonstrated that the type of biomolecular corona can dictate the inhibitory or acceleratory effect of NPs on Aß1-42 and Aß25-35 fibrillation processes. More specifically, we found that the plasma biomolecular-corona-coated gold NPs, with sphere and rod shapes, has less inhibitory effect on Aß1-42 fibrillation kinetics compared with CSF biomolecular-corona-coated and pristine NPs. Opposite results were obtained for Aß25-35 peptide, where the pristine NPs accelerated the Aß25-35 fibrillation process, whereas corona-coated ones demonstrated an inhibitory effect. In addition, the CSF biomolecular corona had less inhibitory effect than those obtained from plasma.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Nanopartículas/química , Fragmentos de Péptidos/metabolismo , Multimerización de Proteína , Péptidos beta-Amiloides/química , Animales , Compuestos de Oro/química , Humanos , Cinética , Fragmentos de Péptidos/química , Agregación Patológica de Proteínas/metabolismo
20.
Sci Rep ; 8(1): 10815, 2018 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-30018335

RESUMEN

The polarization imaging technique is a powerful approach to probe microstructural and optical information of biological structures (e.g., tissue samples). Here, we have studied the polarization properties of different bacterial colonies in order to evaluate the possibility of bacterial detection and discrimination. In this regard, we have taken the backscattering Mueller matrix images of four different bacteria colonies (i.e., Escherichia coli, Lactobacillus rhamnosus, Rhodococcus erythropolis, and Staphylococcus aureus). Although the images have the potential to distinguish qualitatively different bacterial colonies, we explored more accurate and quantitative parameters criteria for discrimination of bacterial samples; more specifically, we have exploited the Mueller matrix polar decomposition (MMPD),frequency distribution histogram (FDH), and central moment analysis method. The outcomes demonstrated a superior capacity of Mueller matrix imaging, MMPD, and FDH in bacterial colonies identification and discrimination. This approach might pave the way for a reliable, efficient, and cheap way of identification of infectious diseases.


Asunto(s)
Escherichia coli/citología , Lacticaseibacillus rhamnosus/citología , Microscopía de Polarización/métodos , Rhodococcus/citología , Staphylococcus aureus/citología , Algoritmos , Escherichia coli/química , Interpretación de Imagen Asistida por Computador , Lacticaseibacillus rhamnosus/química , Rhodococcus/química , Staphylococcus aureus/química
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