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1.
Nat Commun ; 11(1): 5062, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033254

RESUMO

Septins are GTP-binding proteins involved in diverse cellular processes including division and membrane remodeling. Septins form linear, palindromic heteromeric complexes that can assemble in filaments and higher-order structures. Structural studies revealed various septin architectures, but questions concerning assembly-dynamics and -pathways persist. Here we used high-speed atomic force microscopy (HS-AFM) and kinetic modeling which allowed us to determine that septin filament assembly was a diffusion-driven process, while formation of higher-order structures was complex and involved self-templating. Slightly acidic pH and increased monovalent ion concentrations favor filament-assembly, -alignment and -pairing. Filament-alignment and -pairing further favored diffusion-driven assembly. Pairing is mediated by the septin N-termini face, and may occur symmetrically or staggered, likely important for the formation of higher-order structures of different shapes. Multilayered structures are templated by the morphology of the underlying layers. The septin C-termini face, namely the C-terminal extension of Cdc12, may be involved in membrane binding.


Assuntos
Microscopia de Força Atômica , Septinas/metabolismo , Simulação por Computador , Difusão , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Lipídeos/química , Domínios Proteicos , Septinas/ultraestrutura , Eletricidade Estática
2.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 4506-4509, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018995

RESUMO

Smart devices are quickly becoming ubiquitous with the rise of portable biosensors and the internet of things. There exists particular interest in enhancing common objects to have smart capabilities and finding inexpensive solutions for diagnostic tools. One such example is transforming paper items into interactive devices and point-of-care analytic products. Due to the lightweight, flexible, and cost-efficient qualities of paper, unobtrusively powering these devices remains an outstanding problem. In this paper, we demonstrate an electrostatic human-touch powered energy harvesting system, integrated with flexible painted conductive electrodes on paper. This system harvests 8.5 nJ of energy and reaches a voltage of 1.3 V on a 10 nF energy storage capacitor. This technology not only provides a method of powering paper-based products with routine human gestures but can also detect human touch for input communication to sensors.


Assuntos
Eletrônica , Condutividade Elétrica , Eletrodos , Humanos , Fenômenos Físicos , Eletricidade Estática
3.
Nat Commun ; 11(1): 5047, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028810

RESUMO

COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 or MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two cysteine viral proteases essential for viral replication. Our crystallographic screen identified 71 hits that span the entire active site, as well as 3 hits at the dimer interface. These structures reveal routes to rapidly develop more potent inhibitors through merging of covalent and non-covalent fragment hits; one series of low-reactivity, tractable covalent fragments were progressed to discover improved binders. These combined hits offer unprecedented structural and reactivity information for on-going structure-based drug design against SARS-CoV-2 main protease.


Assuntos
Betacoronavirus/química , Cisteína Endopeptidases/química , Fragmentos de Peptídeos/química , Proteínas não Estruturais Virais/química , Betacoronavirus/enzimologia , Sítios de Ligação , Domínio Catalítico , Cristalografia por Raios X , Cisteína Endopeptidases/metabolismo , Desenho de Fármacos , Espectrometria de Massas , Modelos Moleculares , Fragmentos de Peptídeos/metabolismo , Conformação Proteica , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/metabolismo , Eletricidade Estática , Proteínas não Estruturais Virais/metabolismo
4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2520-2523, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018519

RESUMO

Non-contact galvanotaxis as a way to drive the cells migration could be a promising tool for a variety of biomedical applications, such as wound healing control, avoiding the interaction between electrodes and cell cultures. To this regard, the efficacy of this electrical stimulus application has to be deeper studied to control physiological migratory phenomena in a remote way.Aim of this work is to provide an experimental investigation on the mobility of cells exposed to a static electric field in a "noncontact" mode, supported by a suitable modeling of the electric field distribution inside the experimental setup. In particular, scratch assays have been carried out placing the electrodes outside the cells medium support and changing the cells holder to study more than one configuration.Clinical Relevance- In this study the in vitro experiments on the non-contact galvanotaxis, together with the numerical simulations of the exposure setup, provide a way to investigate the effects that could affect an electrically drive cell migration.


Assuntos
Eletricidade , Resposta Táctica , Bioensaio , Movimento Celular , Eletricidade Estática
5.
Biotechniques ; 69(3): 206-210, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32929995

RESUMO

We explore the design of a smart inhaler with electrostatic sterilizer and propose the utilization of cationic amphiphilic peptides, independently or in conjunction with a bronchodilator, for COVID-19 patients to quickly improve wellbeing while maintaining a strategic distance to protect healthcare personnel from virus-containing aerosol or droplets during the process of inhalation.


Assuntos
Anti-Infecciosos/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Nebulizadores e Vaporizadores , Pneumonia Viral/tratamento farmacológico , Eletricidade Estática , Administração por Inalação , Betacoronavirus , Microambiente Celular/efeitos dos fármacos , Humanos , Pulmão/efeitos dos fármacos , Pandemias
6.
Nat Commun ; 11(1): 4896, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32994414

RESUMO

Natural biomolecules such as peptides and DNA can dynamically self-organize into diverse hierarchical structures. Mimicry of this homopolymer self-assembly using synthetic systems has remained limited but would be advantageous for the design of adaptive bio/nanomaterials. Here, we report both experiments and simulations on the dynamic network self-assembly and subsequent collapse of the synthetic homopolymer poly(propylene sulfone). The assembly is directed by dynamic noncovalent sulfone-sulfone bonds that are susceptible to solvent polarity. The hydration history, specified by the stepwise increase in water ratio within lower polarity water-miscible solvents like dimethylsulfoxide, controls the homopolymer assembly into crystalline frameworks or uniform nanostructured hydrogels of spherical, vesicular, or cylindrical morphologies. These electrostatic hydrogels have a high affinity for a wide range of organic solutes, achieving >95% encapsulation efficiency for hydrophilic small molecules and biologics. This system validates sulfone-sulfone bonding for dynamic self-assembly, presenting a robust platform for controllable gelation, nanofabrication, and molecular encapsulation.


Assuntos
Hidrogéis/síntese química , Polipropilenos/síntese química , Sulfonas/química , Alcenos/química , Hidrogéis/química , Interações Hidrofóbicas e Hidrofílicas , Polipropilenos/química , Eletricidade Estática
7.
Chemosphere ; 254: 126905, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32957298

RESUMO

With the development of modern technologies, the exploitation and application of rare earth metals (REMs) have increased parallelly. Consequently, more REMs are entering into the environment and therefore there is a pressing need to assess their potential environmental hazards. Here, a standard toxicity test with wheat (Triticum aestivum) was conducted to investigate the single and mixture toxicity of La and Ce in solutions with different levels of calcium and nitrilotriacetic acid (NTA) and results were deciphered by different modeling approaches. Both La and Ce caused adverse effect to wheat, but the presence of Ca and NTA alleviated their toxicity. The obtained EC50 for [La] or [Ce] changed by more than 28-fold and by 4-fold, respectively, with the increase of Ca or NTA. The biotic ligand model (BLM) explained approximately 93% variation of single La or Ce toxicity. The binding constants obtained were 4.14, 6.67, and 6.59 for logKCaBL, logKLaBL, and logKCeBL respectively. The electrostatic toxicity model (ETM) was proved as effective as the BLM, with R2 = 0.93 for La and R2 = 0.92 for Ce. For La-Ce mixtures, parameters from single toxicity approaches were applied successfully to predict the mixture toxicity with concentration addition (CA) model based on the BLM or ETM theory (R2 = 0.92 and RMSE = 8.56; R2 = 0.90 and RMSE = 9.6, respectively). Thus, the results obtained in this study prove that both ETM and BLM theories are appropriate to predict single and mixture REMs toxicity, providing coherent and promising tools for the risk assessment of REM pollution.


Assuntos
Cálcio/química , Cério/toxicidade , Lantânio/toxicidade , Ácido Nitrilotriacético/química , Testes de Toxicidade/métodos , Triticum/efeitos dos fármacos , Ligantes , Modelos Teóricos , Soluções , Eletricidade Estática , Triticum/crescimento & desenvolvimento
8.
PLoS One ; 15(9): e0238350, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956346

RESUMO

In this study, the effect of surfactants and electrolytes on stability of kaolinite dispersions was analyzed by measuring suspension transmittance, zeta potential, and adsorption. It was experimentally found that the compression of kaolinite electric double layer caused by NaCl addition may reduce the electrostatic repulse force to facilitate the aggregation of kaolinite particles. Surfactant facilitate the aggregation of kaolinite particles mainly through the adsorption of it on the surface of kaolinite to generate hydrophobic force. Compared to anionic surfactant, the cationic surfactant has a better flocculation effect because it can be used in a wide pH range and its adsorption can reduce the electrostatic repulse force between kaolinite particles.


Assuntos
Eletrólitos/química , Caulim/química , Eletricidade Estática , Tensoativos/química , Água/química , Floculação , Concentração de Íons de Hidrogênio
9.
Int J Nanomedicine ; 15: 6167-6182, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922000

RESUMO

Background: Among the novel cancer treatment strategies, combination therapy is a cornerstone of cancer therapy. Materials and Methods: Here, combination therapy with targeted polymer, magnetic hyperthermia and chemotherapy was presented as an effective therapeutic technique. The DOX-loaded PLA-PEG-FA magnetic nanoparticles (nanocarrier) were prepared via a double emulsion method. The nanocarriers were characterized by particle size, zeta potential, morphology, saturation magnetizations and heat generation capacity, and the encapsulation efficiency, drug content and in-vitro drug release for various weight ratios of PLA:DOX. Then, cytotoxicity, cellular uptake and apoptosis level of nanocarrier-treated cells for HeLa and CT26 cells were investigated by MTT assay, flow cytometry, and apoptosis detection kit. Results and Conclusions: The synthesized nanoparticles were spherical in shape, had low aggregation and considerable magnetic properties. Meanwhile, the drug content and encapsulation efficiency of nanoparticles can be achieved by varying the weight ratios of PLA:DOX. The saturation magnetizations of nanocarriers in the maximum applied magnetic field were 59/447 emu/g and 28/224 emu/g, respectively. Heat generation capacity of MNPs and nanocarriers were evaluated in the external AC magnetic field by a hyperthermia device. The highest temperature, 44.2°C, was measured in the nanocarriers suspension at w/w ratio 10:1 (polymer:DOX weight ratio) after exposed to the magnetic field for 60 minutes. The encapsulation efficiency improved with increasing polymer concentration, since the highest DOX encapsulation efficiency was related to the nanocarriers' suspension at w/w ratio 50:1 (79.6 ± 6.4%). However, the highest DOX loading efficiency was measured in the nanocarriers' suspension at w/w ratio 10:1 (5.14 ± 0.6%). The uptake efficiency and apoptosis level of nanocarrier-treated cells were higher than those of nanocarriers (folic acid free) and free DOX-treated cells in both cell lines. Therefore, this targeted nanocarrier may offer a promising nanosystem for cancer-combined chemotherapy and hyperthermia.


Assuntos
Doxorrubicina/farmacologia , Ácido Fólico/farmacologia , Hipertermia Induzida , Nanopartículas de Magnetita/química , Neoplasias/terapia , Polietilenoglicóis/química , Animais , Apoptose/efeitos dos fármacos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Células HeLa , Humanos , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Tamanho da Partícula , Polietilenoglicóis/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática
10.
Nat Commun ; 11(1): 4768, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958747

RESUMO

Detection and identification of proteins are typically achieved by analyzing protein size, charge, mobility and binding to antibodies, which are critical for biomedical research and disease diagnosis and treatment. Despite the importance, measuring these quantities with one technology and at the single-molecule level has not been possible. Here we tether a protein to a surface with a flexible polymer, drive it into oscillation with an electric field, and image the oscillation with a near field optical imaging method, from which we determine the size, charge, and mobility of the protein. We also measure antibody binding and conformation changes in the protein. The work demonstrates a capability for comprehensive protein analysis and precision protein biomarker detection at the single molecule level.


Assuntos
Proteínas/química , Proteínas/metabolismo , Imagem Individual de Molécula/métodos , Análise de Fourier , Ligantes , Polietilenoglicóis/química , Ligação Proteica , Conformação Proteica , Eletricidade Estática , Compostos de Estanho/química
11.
PLoS One ; 15(8): e0236409, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853253

RESUMO

This paper proposes an alternative approach to extract transformer's winding parameters of resistance (R), inductance (L), capacitance (C) and conductance (G) based on Finite Element Method (FEM). The capacitance and conductance were computed based on Fast Multiple Method (FMM) and Method of Moment (MoM) through quasi-electrostatics approach. The AC resistances and inductances were computed based on MoM through quasi-magnetostatics approach. Maxwell's equations were used to compute the DC resistances and inductances. Based on the FEM computed parameters, the frequency response of the winding was obtained through the Bode plot function. The simulated frequency response by FEM model was compared with the simulated frequency response based on the Multi-conductor Transmission Line (MTL) model and the measured frequency response of a 33/11 kV, 30 MVA transformer. The statistical indices such as Root Mean Square Error (RMSE) and Absolute Sum of Logarithmic Error (ASLE) were used to analyze the performance of the proposed FEM model. It is found that the simulated frequency response by FEM model is quite close to measured frequency response at low and mid frequency regions as compared to simulated frequency response by MTL model based on RMSE and ASLE analysis.


Assuntos
Capacitância Elétrica , Fontes de Energia Elétrica , Análise de Elementos Finitos , Simulação por Computador , Condutividade Elétrica , Eletricidade Estática
12.
J Phys Chem B ; 124(34): 7336-7347, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32790406

RESUMO

The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, was declared a pandemic by the World Health Organization in March 2020. Genetically, SARS-CoV-2 is closely related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries from 2002 to 2003. Given the significant morbidity and mortality rate, the current pandemic poses a danger to all of humanity, prompting us to understand the activity of SARS-CoV-2 at the atomic level. Experimental studies have revealed that spike proteins of both SARS-CoV-2 and SARS-CoV bind to angiotensin-converting enzyme 2 (ACE2) before entering the cell for replication. However, the binding affinities reported by different groups seem to contradict each other. Wrapp et al. (Science 2020, 367, 1260-1263) showed that the spike protein of SARS-CoV-2 binds to the ACE2 peptidase domain (ACE2-PD) more strongly than does SARS-CoV, and this fact may be associated with a greater severity of the new virus. However, Walls et al. (Cell 2020, 181, 281-292) reported that SARS-CoV-2 exhibits a higher binding affinity, but the difference between the two variants is relatively small. To understand the binding mechnism and experimental results, we investigated how the receptor binding domain (RBD) of SARS-CoV (SARS-CoV-RBD) and SARS-CoV-2 (SARS-CoV-2-RBD) interacts with a human ACE2-PD using molecular modeling. We applied a coarse-grained model to calculate the dissociation constant and found that SARS-CoV-2 displays a 2-fold higher binding affinity. Using steered all-atom molecular dynamics simulations, we demonstrate that, like a coarse-grained simulation, SARS-CoV-2-RBD was associated with ACE2-PD more strongly than was SARS-CoV-RBD, as evidenced by a higher rupture force and larger pulling work. We show that the binding affinity of both viruses to ACE2 is driven by electrostatic interactions.


Assuntos
Betacoronavirus/química , Peptidil Dipeptidase A/metabolismo , Receptores Virais/metabolismo , Vírus da SARS/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Humanos , Simulação de Dinâmica Molecular , Mutação , Ligação Proteica , Glicoproteína da Espícula de Coronavírus/genética , Eletricidade Estática
13.
Sci Transl Med ; 12(557)2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32747425

RESUMO

Pathogenic coronaviruses are a major threat to global public health, as exemplified by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound 1 day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Inibidores de Proteases/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/química , Betacoronavirus/fisiologia , Linhagem Celular , Chlorocebus aethiops , Infecções por Coronavirus/patologia , Cristalografia por Raios X , Cisteína Endopeptidases/química , Modelos Animais de Doenças , Humanos , Técnicas In Vitro , Pulmão/patologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Transgênicos , Testes de Sensibilidade Microbiana , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Modelos Moleculares , Pandemias , Inibidores de Proteases/química , Bibliotecas de Moléculas Pequenas , Especificidade da Espécie , Eletricidade Estática , Pesquisa Médica Translacional , Células Vero , Carga Viral/efeitos dos fármacos , Proteínas não Estruturais Virais/química
14.
Int J Nanomedicine ; 15: 5671-5685, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821096

RESUMO

Aim: The aim of the current work was to develop vardenafil hydrochloride (VRD)-loaded ethosome-derived invasomes as a possible transdermal system which could be used for patients suffering from pulmonary arterial hypertension. Methods: VRD-loaded ethosomes were developed at three concentrations of phosphatidylcholine (5, 10 and 15 mg/mL) and three percentages of ethanol (20%, 30% and 40%, v/v). The best achieved VRD-loaded ethosomes (ETH9) were optimized to invasomes via incorporation of terpenes (limonene, cineole and a 1:1 mixture) at three concentrations (0.5%, 1% and 2%, v/v). All systems were evaluated for vesicle size, zeta potential, drug entrapment efficiency (EE%), cumulative drug permeated percentages after 0.5hrs (Q0.5h) and 12hrs (Q12h) and steady-state flux (Jss). The optimized system (ETH9-INV8) was further characterized for morphology, histopathology and confocal laser scanning microscopy (CLSM). Physiologically based pharmacokinetic (PBPK) modeling was employed to estimate VRD pharmacokinetic parameters from the optimized transdermal system and an oral aqueous drug dispersion, in adults and geriatrics. Results: The optimized invasomal system (ETH9-INV8) was characterized with spherical vesicles (159.9 nm) possessing negative zeta potential (-20.3 mV), promising EE% (81.3%), low Q0.5h (25.4%), high Q12h (85.3%) and the largest steady-state flux (6.4 µg.cm-2h-1). Following a leave-on period of 12hrs in rats, it showed minor histopathologic changes. CLSM studies proved its ability to deeply permeate rat skin. Lower Cmax values, delayed Tmax estimates and greater AUC0-24h folds in adults and geriatrics (≈ 2.18 and 1.69, respectively) were estimated following the transdermal application of ETH9-INV8 system. Conclusion: ETH9-INV8 is a promising transdermal system for VRD.


Assuntos
Sistemas de Liberação de Medicamentos , Etanol/química , Geriatria , Modelos Biológicos , Dicloridrato de Vardenafila/administração & dosagem , Dicloridrato de Vardenafila/farmacocinética , Administração Cutânea , Animais , Lipossomos , Masculino , Microscopia Confocal , Tamanho da Partícula , Permeabilidade , Ratos Wistar , Absorção Cutânea , Eletricidade Estática
15.
BMC Bioinformatics ; 21(Suppl 10): 354, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32838732

RESUMO

BACKGROUND: Type A influenza viruses circulate and spread among wild birds and mostly consist of low pathogenic strains. However, fast genome variation timely results in the insurgence of high pathogenic strains, which when infecting poultry birds may cause a million deaths and strong commercial damage. More importantly, the host shift may concern these viruses and sustained human-to-human transmission may result in a dangerous pandemic outbreak. Therefore, fingerprints specific to either low or high pathogenic strains may represent a very important tool for global surveillance. RESULTS: We combined Normal Modes Analysis and surface electrostatic analysis of a mixed strain dataset of influenza A virus haemagglutinins from high and low pathogenic strains in order to infer specific fingerprints. Normal Modes Analysis sorted the strains in two different, homogeneous clusters; sorting was independent of clades and specific instead to high vs low pathogenicity. A deeper analysis of fluctuations and flexibility regions unveiled a special role for the 110-helix region. Specific sorting was confirmed by surface electrostatics analysis, which further allowed to focus on regions and mechanisms possibly crucial to the low-to-high transition. CONCLUSIONS: Evidence from previous work demonstrated that changes in surface electrostatics are associated with the evolution and spreading of avian influenza A virus clades, and seemingly involved also in the avian to mammalian host shift. This work shows that a combination of electrostatics and Normal Modes Analysis can also identify fingerprints specific to high and low pathogenicity. The possibility to predict which specific mutations may result in a shift to high pathogenicity may help in surveillance and vaccine development.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A/metabolismo , Vírus da Influenza A/patogenicidade , Eletricidade Estática , Algoritmos , Animais , Animais Selvagens/virologia , Aves/virologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Influenza Aviária/virologia , Modelos Moleculares , Domínios Proteicos
16.
J Med Life ; 13(2): 195-199, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742513

RESUMO

Polyurethane nano- and micro-structures have been studied intensively in the last decade as drug delivery systems for various herbal extracts as well as pure active biological substances. Their biocompatibility, haemocompatibility, safe degradation, and low-cost production are just a few advantages of these materials that were already used in numerous medical applications (catheters, surgical drapes, wound dressing). The primary purposes of this study include obtaining empty polyurethane microstructures and the assessment of their modifications in media with different pH values. A mixture of two aliphatic diisocyanates and an aqueous phase based on a polyether were used during the synthesis process. The size, homogeneity, and surface charge were studied using a Cordouan Technol. Zetasizer, while the pH measurements were conducted with a portable pH Meter Checker®, Hanna Instruments. The results showed the obtaining of an almost homogeneous sample containing microstructures with sizes ranging between 139 and 151 nm, with a pH value of approximately 6.78 and a Zeta potential of 24.6. Expected decreases in microparticles' sizes were observed in all types of media during a 15-days experiment, but the process was accelerated by a low pH when an increase of the Zeta potential value was noticed as well. Our data provide new information about the degradation process of the polyurethane microstructures on the one hand and the drug release rate of these materials when used as drug carriers, on the other hand.


Assuntos
Portadores de Fármacos/química , Poliuretanos/química , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Eletricidade Estática
17.
J Nanosci Nanotechnol ; 20(12): 7311-7323, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32711596

RESUMO

We started a study on the molecular docking of six potential pharmacologically active inhibitors compounds that can be used clinically against the COVID-19 virus, in this case, remdesivir, ribavirin, favipiravir, galidesivir, hydroxychloroquine and chloroquine interacting with the main COVID-19 protease in complex with a COVID-19 N3 protease inhibitor. The highest values of affinity energy found in order from highest to lowest were chloroquine (CHL), hydroxychloroquine (HYC), favipiravir (FAV), galidesivir (GAL), remdesivir (REM) and ribavirin (RIB). The possible formation of hydrogen bonds, associations through London forces and permanent electric dipole were analyzed. The values of affinity energy obtained for the hydroxychloroquine ligands was -9.9 kcal/mol and for the chloroquine of -10.8 kcal/mol which indicate that the coupling contributes to an effective improvement of the affinity energies with the protease. Indicating that, the position chosen to make the substitutions may be a pharmacophoric group, and cause changes in the protease.


Assuntos
Antivirais/química , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/enzimologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Cisteína Endopeptidases/química , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/química , Adenina/administração & dosagem , Adenina/análogos & derivados , Adenina/química , Adenina/farmacologia , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/química , Monofosfato de Adenosina/farmacologia , Alanina/administração & dosagem , Alanina/análogos & derivados , Alanina/química , Alanina/farmacologia , Amidas/administração & dosagem , Amidas/química , Amidas/farmacologia , Antivirais/administração & dosagem , Sítios de Ligação , Cloroquina/administração & dosagem , Cloroquina/química , Cloroquina/farmacologia , Interações Medicamentosas , Humanos , Ligação de Hidrogênio , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/química , Hidroxicloroquina/farmacologia , Ligantes , Simulação de Acoplamento Molecular , Nanotecnologia , Pandemias , Inibidores de Proteases/administração & dosagem , Pirazinas/administração & dosagem , Pirazinas/química , Pirazinas/farmacologia , Pirrolidinas/administração & dosagem , Pirrolidinas/química , Pirrolidinas/farmacologia , Ribavirina/administração & dosagem , Ribavirina/química , Ribavirina/farmacologia , Eletricidade Estática
18.
PLoS Comput Biol ; 16(7): e1007801, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32628657

RESUMO

Recent experiments with super-resolution live cell microscopy revealed that nonmuscle myosin II minifilaments are much more dynamic than formerly appreciated, often showing plastic processes such as splitting, concatenation and stacking. Here we combine sequence information, electrostatics and elasticity theory to demonstrate that the parallel staggers at 14.3, 43.2 and 72 nm have a strong tendency to splay their heads away from the minifilament, thus potentially initiating the diverse processes seen in live cells. In contrast, the straight antiparallel stagger with an overlap of 43 nm is very stable and likely initiates minifilament nucleation. Using stochastic dynamics in a newly defined energy landscape, we predict that the optimal parallel staggers between the myosin rods are obtained by a trial-and-error process in which two rods attach and re-attach at different staggers by rolling and zipping motion. The experimentally observed staggers emerge as the configurations with the largest contact times. We find that contact times increase from isoforms C to B to A, that A-B-heterodimers are surprisingly stable and that myosin 18A should incorporate into mixed filaments with a small stagger. Our findings suggest that nonmuscle myosin II minifilaments in the cell are first formed by isoform A and then convert to mixed A-B-filaments, as observed experimentally.


Assuntos
Miosina Tipo II , Eletricidade Estática , Biologia Computacional , Humanos , Modelos Moleculares , Miosina Tipo II/química , Miosina Tipo II/metabolismo , Miosina Tipo II/ultraestrutura , Conformação Proteica , Isoformas de Proteínas
19.
Int J Nanomedicine ; 15: 4049-4062, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606663

RESUMO

Background: Calcium carbonate (CC) nanoparticles have broad biomedical utilizations, owing to their multiple intrinsic merits. However, bare CC nanoparticles do not allow for the development of multifunctional devices suitable for advanced drug delivery in cancer therapy. Methods: Phospholipid-modified phospholipid-CC hybrid nanoparticles were prepared in our study using a combination of vapor-diffusion and solvent-diffusion methods to offer optimized pharmaceutical capabilities. Results: Considering that particle size is a critical parameter that plays an important role in both in vitro and in vivo behaviors of nanoparticles, we here for the first time a present detailed protocol for the size-controlled preparation of hybrid nanoparticles, as well as analysis of the in vitro/in vivo behaviors of differently sized hybrid nanoparticles. Conclusion: Our results might significantly advance the application of this promising material in more varied fields.


Assuntos
Carbonato de Cálcio/química , Nanopartículas/química , Tamanho da Partícula , Fosfolipídeos/química , Animais , Linhagem Celular , Permeabilidade da Membrana Celular , Sistemas de Liberação de Medicamentos/métodos , Endocitose , Feminino , Humanos , Lisossomos/metabolismo , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Coelhos , Esferoides Celulares/metabolismo , Eletricidade Estática , Temperatura , Fatores de Tempo , Distribuição Tecidual
20.
Int J Nanomedicine ; 15: 4523-4540, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606692

RESUMO

Purpose: Selenium nanoparticles (SeNP) have several applications in the field of biotechnology, including their use as anti-cancer drugs. The purpose of the present study is to analyze the efficacy of green synthesis on the preparation of SeNP and its effect on their anti-cancer properties. Methods: A bacterial strain isolated from a freshwater source was shown to efficiently synthesize SeNP with potential therapeutic properties. The quality and stability of the NP were studied by scanning electron microscopy, X-ray diffraction, zeta-potential and FTIR analysis. A cost-effective medium formulation from biowaste having 6% banana peel extract enriched with 0.25 mM tryptophan was used to synthesize the NP. The NP after optimization was used to analyze their anti-tumor and anti-angiogenic activity. For this purpose, first, the cytotoxicity of the NP against cancer cells was analyzed by MTT assay and then chorioallantoic membrane assay was performed to assess anti-angiogenic activity. Further, cell migration assay and clonogenic inhibition assay were performed to test the anti-tumor properties of SeNP. To assess the cytotoxicity of SeNP on healthy RBC, hemolysis assay was performed. Results: The strain identified as Pseudomonas stutzeri (MH191156) produced phenazine carboxylic acid, which aids the conversion of Se oxyanions to reduced NP state, resulting in particles in the size range of 75 nm to 200 nm with improved stability and quality of SeNP, as observed by zeta (ξ) potential of the particles which was found to be -46.2 mV. Cytotoxicity of the SeNP was observed even at low concentrations such as 5 µg/mL against cervical cancer cell line, ie, HeLa cells. Further, neovascularization was inhibited by upto 30 % in CAMs of eggs coinoculated with SeNp when compared with untreated controls, indicating significant anti-angiogenic activity of SeNP. The NP also inhibited the invasiveness of HeLa cells as observed by decreased cell migration and clonogenic proliferation. These observations indicate significant anti-tumor and anti-angiogenic activity of the SeNP in cervical cancer cells. Conclusion: P. stutzeri (MH191156) is an efficient source of Se NP production with potential anti-angiogenic and anti-tumor properties, particularly against cervical cancer cells.


Assuntos
Inibidores da Angiogênese/farmacologia , Nanopartículas Metálicas/química , Pseudomonas stutzeri/metabolismo , Selênio/farmacologia , Animais , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Custos e Análise de Custo , Feminino , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Nanopartículas Metálicas/ultraestrutura , Fenazinas/química , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Neoplasias do Colo do Útero/irrigação sanguínea , Neoplasias do Colo do Útero/patologia , Difração de Raios X
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