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1.
J Nanobiotechnology ; 18(1): 125, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891146

RESUMO

Incidents of viral outbreaks have increased at an alarming rate over the past decades. The most recent human coronavirus known as COVID-19 (SARS-CoV-2) has already spread around the world and shown R0 values from 2.2 to 2.68. However, the ratio between mortality and number of infections seems to be lower in this case in comparison to other human coronaviruses (such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)). These outbreaks have tested the limits of healthcare systems and have posed serious questions about management using conventional therapies and diagnostic tools. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. In this review, we discuss the use of nanotechnology for COVID-19 virus management by the development of nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and nanocarrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanotecnologia/métodos , Pandemias , Pneumonia Viral , Antivirais/administração & dosagem , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Desinfecção/métodos , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Humanos , Nanoestruturas/administração & dosagem , Equipamento de Proteção Individual , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Vacinas Virais/administração & dosagem
2.
Mater Sci Eng C Mater Biol Appl ; 117: 111330, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32919683

RESUMO

Nanomotors, multimetallic systems are biologically inspired self-propelled tiny engines able to perform difficult tasks of transporting cargos from one end to another in presence of hydrogen peroxide fuel. Nanomotors can revolutionize the drug delivery system at the desired target by converting chemical energy into mechanical energy. Nanomotors exhibit unique properties like moving at higher speed, self-propulsion and drilling into the complex cellular environment. The review focuses on fuel dependent and fuel-free nanomotors with their propulsion mechanism. Further, the review highlights the method of fabrication, biohybrid nanomotors, toxicities along with their application in the field of active drug delivery, diabetes, precise surgery, ischemic stroke therapy, diagnosis and treatment of coronavirus, microwave hyperthermia, zika virus detection, anti-bacterial activity, water treatment and sensing and challenges lying at the forefront in the development of these tiny nanomachines. Hydrogen peroxide is toxic to mankind; biohybrid motors give an extra edge of eliminating hydrogen peroxide as fuel for self-propulsion, this can be used for smart drug delivery by reducing toxicities as compared to artificial nanomotors. Cost-effective fabrication of nanomotors will extend their applications in commercial sector overcoming limitations like scale-up and regulatory approval. In near future, nanomotors will diversify in fields of restoring conductivity of electronic medical devices, 3D printing and theranostics.


Assuntos
Assistência à Saúde , Nanotecnologia , Pesquisa Biomédica , Catálise , Infecções por Coronavirus/terapia , Humanos , Pandemias , Pneumonia Viral/terapia , Impressão Tridimensional
3.
Nat Commun ; 11(1): 4714, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948754

RESUMO

The application of forces and torques on the single molecule level has transformed our understanding of the dynamic properties of biomolecules, but rare intermediates have remained difficult to characterize due to limited throughput. Here, we describe a method that provides a 100-fold improvement in the throughput of force spectroscopy measurements with topological control, which enables routine imaging of 50,000 single molecules and a 100 million reaction cycles in parallel. This improvement enables detection of rare events in the life cycle of the cell. As a demonstration, we characterize the supercoiling dynamics and drug-induced DNA break intermediates of topoisomerases. To rapidly quantify distinct classes of dynamic behaviors and rare events, we developed a software platform with an automated feature classification pipeline. The method and software can be readily adapted for studies of a broad range of complex, multistep enzymatic pathways in which rare intermediates have escaped classification due to limited throughput.


Assuntos
DNA/química , Fenômenos Magnéticos , Magnetismo/métodos , Nanotecnologia , Análise Espectral/métodos , Ciprofloxacino/farmacologia , DNA/efeitos dos fármacos , Quebras de DNA/efeitos dos fármacos , Conformação de Ácido Nucleico , Pinças Ópticas , Fenômenos Físicos , Software
4.
Nat Commun ; 11(1): 4384, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873796

RESUMO

The ability to detect low concentrations of biomarkers in patient samples is one of the cornerstones of modern healthcare. In general, biosensing approaches are based on measuring signals resulting from the interaction of a large ensemble of molecules with the sensor. Here, we report a biosensor platform using DNA origami featuring a central cavity with a target-specific DNA aptamer coupled with a nanopore read-out to enable individual biomarker detection. We show that the modulation of the ion current through the nanopore upon the DNA origami translocation strongly depends on the presence of the biomarker in the cavity. We exploit this to generate a biosensing platform with a limit of detection of 3 nM and capable of the detection of human C-reactive protein (CRP) in clinically relevant fluids. Future development of this approach may enable multiplexed biomarker detection by using ribbons of DNA origami with integrated barcoding.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/instrumentação , DNA/química , Nanoestruturas/química , Imagem Individual de Molécula/instrumentação , Biomarcadores/análise , Proteína C-Reativa/análise , Desenho de Equipamento , Humanos , Limite de Detecção , Nanotecnologia/métodos
5.
J Environ Manage ; 275: 111234, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32866924

RESUMO

Effective and efficient utilization of antimicrobial drugs has been one of the important cornerstone of modern medicine. However, since antibiotics were first discovered by Alexander Fleming about a century ago, the time clock of antimicrobial resistance (AMR) started ticking somewhat leading to a global fear of a possible "post-antimicrobial era". Antibiotic resistance (AR) remains a serious challenge causing global outcry in both the clinical setting and the environment. The huge influence of municipal wastewater effluent discharges on the aquatic environment has made the niche a hotspot of research interest in the study of emergence and spread of AMR microbes and their resistance determinants/genes. The current review adopted a holistic approach in studying the proliferation of antibiotic resistance determinants (ARDs) as well as their impacts and fate in municipal wastewater effluents and the receiving aquatic environments. The various strategies deployed hitherto for the removal of resistance determinants in municipal effluents were carefully reviewed, while the potential for the use of nanotechnology as a viable alternative is explicitly explored. Also, highlighted in this review are the knowledge gaps to be filled in order to curtail the spread of AMR in aquatic environment and lastly, suggestions on the applicability of nanotechnology in eliminating AMR determinants in municipal wastewater treatment facilities are proffered.


Assuntos
Antibacterianos , Anti-Infecciosos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Nanotecnologia , Águas Residuárias
6.
Anal Chem ; 92(19): 13396-13404, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32867467

RESUMO

Rapid, accurate, reliable, and risk-free tracking of pathogenic microorganisms at the single-cell level is critical to achieve efficient source control and prevent outbreaks of microbial infectious diseases. For the first time, we report a promising approach for integrating the concepts of a remarkably large Stokes shift and dual-recognition into a single matrix to develop a pathogenic microorganism stimuli-responsive ratiometric fluorescent nanoprobe with speed, cost efficiency, stability, ultrahigh specificity, and sensitivity. As a proof-of-concept, we selected the Gram-positive bacterium Staphylococcus aureus (S. aureus) as the target analyte model, which easily bound to its recognition aptamer and the broad-spectrum glycopeptide antibiotic vancomycin (Van). To improve the specificity and short sample-to-answer time, we employed classic noncovalent π-π stacking interactions as a driving force to trigger the binding of Van and aptamer dual-functionalized near-infrared (NIR) fluorescent Apt-Van-QDs to the surface of an unreported blue fluorescent π-rich electronic carbon nanoparticles (CNPs), achieving S. aureus stimuli-responsive ratiometric nanoprobe Apt-Van-QDs@CNPs. In the assembly of Apt-Van-QDs@CNPs, the blue CNPs (energy donor) and NIR Apt-Van-QDs (energy acceptor) became close to allow the fluorescence resonance energy transfer (FRET) process, leading to a remarkable blue fluorescence quenching for the CNPs at ∼465 nm and a clear NIR fluorescence enhancement for Apt-Van-QDs at ∼725 nm. In the presence of S. aureus, the FRET process from CNPs to Apt-Van-QDs was disrupted, causing the nanoprobe Apt-Van-QDs@CNPs to display a ratiometric fluorescent response to S. aureus, which exhibited a large Stokes shift of ∼260 nm and rapid sample-to-answer detection time (∼30.0 min). As expected, the nanoprobe Apt-Van-QDs@CNPs showed an ultrahigh specificity for ratiometric fluorescence detection of S. aureus with a good detection limit of 1.0 CFU/mL, allowing the assay at single-cell level. Moreover, we also carried out the precise analysis of S. aureus in actual samples with acceptable results. We believe that this work offers new insight into the rational design of efficient ratiometric nanoprobes for rapid on-site accurate screening of pathogenic microorganisms at the single-cell level in the early stages, especially during the worldwide spread of COVID-19 today.


Assuntos
Bactérias/química , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/síntese química , Nanotecnologia/métodos , Antibacterianos/farmacologia , Aptâmeros de Nucleotídeos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/microbiologia , Fluorescência , Transferência Ressonante de Energia de Fluorescência , Microbiologia de Alimentos/métodos , Humanos , Nanopartículas , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/microbiologia , Sensibilidade e Especificidade , Espectroscopia de Luz Próxima ao Infravermelho , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/química , Vancomicina/farmacologia
7.
Adv Healthc Mater ; 9(19): e2000979, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32885616

RESUMO

Researchers, engineers, and medical doctors are made aware of the severity of the COVID-19 infection and act quickly against the coronavirus SARS-CoV-2 using a large variety of tools. In this review, a panoply of nanoscience and nanotechnology approaches show how these disciplines can help the medical, technical, and scientific communities to fight the pandemic, highlighting the development of nanomaterials for detection, sanitation, therapies, and vaccines. SARS-CoV-2, which can be regarded as a functional core-shell nanoparticle (NP), can interact with diverse materials in its vicinity and remains attached for variable times while preserving its bioactivity. These studies are critical for the appropriate use of controlled disinfection systems. Other nanotechnological approaches are also decisive for the development of improved novel testing and diagnosis kits of coronavirus that are urgently required. Therapeutics are based on nanotechnology strategies as well and focus on antiviral drug design and on new nanoarchitectured vaccines. A brief overview on patented work is presented that emphasizes nanotechnology applied to coronaviruses. Finally, some comments are made on patents of the initial technological responses to COVID-19 that have already been put in practice.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanotecnologia/métodos , Pandemias , Pneumonia Viral , Antivirais/administração & dosagem , Betacoronavirus/química , Betacoronavirus/ultraestrutura , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Desinfecção/métodos , Humanos , Nanopartículas/química , Nanopartículas/ultraestrutura , Nanoestruturas/química , Nanotecnologia/legislação & jurisprudência , Pandemias/prevenção & controle , Patentes como Assunto , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Propriedades de Superfície , Vacinas Virais/administração & dosagem
8.
Nat Commun ; 11(1): 4271, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32848153

RESUMO

Performing multi-color nanoscopy for extended times is challenging due to the rapid photobleaching rate of most fluorophores. Here we describe a new fluorophore (Yale-595) and a bio-orthogonal labeling strategy that enables two-color super-resolution (STED) and 3D confocal imaging of two organelles simultaneously for extended times using high-density environmentally sensitive (HIDE) probes. Because HIDE probes are small, cell-permeant molecules, they can visualize dual organelle dynamics in hard-to-transfect cell lines by super-resolution for over an order of magnitude longer than with tagged proteins. The extended time domain possible using these tools reveals dynamic nanoscale targeting between different organelles.


Assuntos
Corantes Fluorescentes , Microscopia de Fluorescência/métodos , Nanotecnologia/métodos , Organelas/metabolismo , Linhagem Celular , Corantes Fluorescentes/química , Células HeLa , Células Endoteliais da Veia Umbilical Humana , Humanos , Imageamento Tridimensional , Microscopia Confocal , Fotodegradação , Imagem com Lapso de Tempo
9.
Nat Commun ; 11(1): 4259, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32848156

RESUMO

The plasma membrane is the interface through which cells interact with their environment. Membrane proteins are embedded in the lipid bilayer of the plasma membrane and their function in this context is often linked to their specific location and dynamics within the membrane. However, few methods are available to manipulate membrane protein location at the single-molecule level. Here, we use fluorescent magnetic nanoparticles (FMNPs) to track membrane molecules and to control their movement. FMNPs allow single-particle tracking (SPT) at 10 nm and 5 ms spatiotemporal resolution, and using a magnetic needle, we pull membrane components laterally with femtonewton-range forces. In this way, we drag membrane proteins over the surface of living cells. Doing so, we detect barriers which we could localize to the submembrane actin cytoskeleton by super-resolution microscopy. We present here a versatile approach to probe membrane processes in live cells via the magnetic control of membrane protein motion.


Assuntos
Nanopartículas de Magnetita , Proteínas de Membrana/metabolismo , Citoesqueleto de Actina/metabolismo , Animais , Linhagem Celular , Chlorocebus aethiops , Proteínas de Fluorescência Verde/metabolismo , Campos Magnéticos , Lipídeos de Membrana/metabolismo , Microscopia de Fluorescência , Nanotecnologia , Imagem Individual de Molécula/métodos
10.
Biosens Bioelectron ; 166: 112471, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32777726

RESUMO

The infection and spread of pathogens (e.g., COVID-19) pose an enormous threat to the safety of human beings and animals all over the world. The rapid and accurate monitoring and determination of pathogens are of great significance to clinical diagnosis, food safety and environmental evaluation. In recent years, with the evolution of nanotechnology, nano-sized graphene and graphene derivatives have been frequently introduced into the construction of biosensors due to their unique physicochemical properties and biocompatibility. The combination of biomolecules with specific recognition capabilities and graphene materials provides a promising strategy to construct more stable and sensitive biosensors for the detection of pathogens. This review tracks the development of graphene biosensors for the detection of bacterial and viral pathogens, mainly including the preparation of graphene biosensors and their working mechanism. The challenges involved in this field have been discussed, and the perspective for further development has been put forward, aiming to promote the development of pathogens sensing and the contribution to epidemic prevention.


Assuntos
Bactérias/isolamento & purificação , Betacoronavirus/isolamento & purificação , Técnicas Biossensoriais/métodos , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Grafite , Pandemias , Pneumonia Viral/diagnóstico , Vírus/isolamento & purificação , Animais , Bactérias/genética , Bactérias/patogenicidade , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Grafite/química , Humanos , Técnicas de Diagnóstico Molecular , Nanotecnologia , Vírus/genética , Vírus/patogenicidade
11.
Int J Nanomedicine ; 15: 5745-5765, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821099

RESUMO

Glaucoma is a group of diseases characterized by progressive degeneration of retinal ganglion cells, leading to irreversible blindness. Currently, intraocular pressure reduction is the only established treatment available for glaucoma. With this treatment, the progression of the disease can only be delayed and there is no recovery. In addition, the commercially available eye drops have the disadvantage of low compliance and short therapeutic time, while glaucoma surgery always has the risk of failure due to wound fibrosis. Nanotechnology can overcome the limitations of the current treatment through the encapsulation and conjugation of drugs used for lowering intraocular pressure and antifibrotic agents using biodegradable or biocompatible nanoparticles for the sustained release of the drugs to protect the damaged ocular cells. Furthermore, using nanotechnology, treatment can be administered in various forms, including eye drops, contact lens, and ocular inserts, according to the convenience of the patients. Despite the promising results of delaying the progression of glaucoma, the regeneration of damaged ocular cells, including trabecular meshwork and retinal ganglion cells, is another critical hurdle to overcome. Bone marrow-derived mesenchymal stem cells and Müller glia cells can secrete neurogenic factors that trigger the regeneration of associated cells, including trabecular meshwork and retinal ganglion cells. In conclusion, this review highlights the potential therapeutic applications of nanotechnology- and stem cell-based methods that can be employed for the protection and regeneration of ocular cells.


Assuntos
Glaucoma/terapia , Nanomedicina , Animais , Lentes de Contato , Sistemas de Liberação de Medicamentos , Glaucoma/etiologia , Humanos , Nanotecnologia , Malha Trabecular/patologia
12.
Int J Nanomedicine ; 15: 5767-5781, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821100

RESUMO

Mammalian target of rapamycin (mTOR) is a master regulator of cell growth and metabolism, which is activated in response to intra- and extracellular signals, including nutrients, growth factors, and cellular energy levels. The frequent dysregulation of mTOR signaling in cancer makes it an attractive therapeutic target, and several types of mTOR inhibitors have been developed. Nanoparticle-based mTOR modulators are predicted to target various cancers and deliver as well as release drugs in a controlled manner, resulting in enhanced bioavailability and reduced side effects. This mini-review is focused on the molecular mechanism of nanoparticle-based mTOR modulator action as well as the current development of mTOR inhibitors using nanoparticles. Understanding the biological function of nanoparticle-based mTOR modulators will contribute to the development of efficient nano-therapeutics for the treatment of cancers.


Assuntos
Terapia de Alvo Molecular , Nanotecnologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Humanos , Neoplasias/patologia
13.
Crit Rev Ther Drug Carrier Syst ; 37(3): 271-303, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749140

RESUMO

Nanotechnology has made great contributions in the development of materials with potential application in different areas, especially in the pharmaceutical sector, where nano-systems are being intensely studied for controlled drug release. These innovative systems are composed of structures such as nanoparticles, nanoemulsions, and cyclodextrins, with the aim of promoting enhanced bioavailability of bioactive molecules. Among these nanocarriers, vesicles such as liposomes and polymersomes are considered to be promising alternatives in delivering hydrophilic and lipophilic drugs. They have different classifications according to their composition, among which are hybrid vesicles, which unlike liposomes are composed of both lipids and polymers. These vesicular systems stand out for combining the advantages of both components, overcoming the limitations of traditional systems imposed by low stability and premature release of the encapsulated active substance. The polymers applied in hybrid vesicles can make up the membrane structure itself or be employed to coat preformed vesicles. Due to the relevance of these systems, this work covers their characteristics and summarizes recent articles about them in the literature.


Assuntos
Cosméticos/administração & dosagem , Lipídeos/administração & dosagem , Nanopartículas/administração & dosagem , Nanotecnologia/métodos , Polímeros/administração & dosagem , Nanomedicina Teranóstica/métodos , Animais , Cosméticos/química , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos/métodos , Humanos , Lipídeos/química , Lipossomos/administração & dosagem , Lipossomos/química , Nanopartículas/química , Polímeros/química
14.
Molecules ; 25(15)2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32731428

RESUMO

In 2020, the world is being ravaged by the coronavirus, SARS-CoV-2, which causes a severe respiratory disease, Covid-19. Hundreds of thousands of people have succumbed to the disease. Efforts at curing the disease are aimed at finding a vaccine and/or developing antiviral drugs. Despite these efforts, the WHO warned that the virus might never be eradicated. Countries around the world have instated non-pharmaceutical interventions such as social distancing and wearing of masks in public to curb the spreading of the disease. Antiviral polysaccharides provide the ideal opportunity to combat the pathogen via pharmacotherapeutic applications. However, a layer-by-layer nanocoating approach is also envisioned to coat surfaces to which humans are exposed that could harbor pathogenic coronaviruses. By coating masks, clothing, and work surfaces in wet markets among others, these antiviral polysaccharides can ensure passive prevention of the spreading of the virus. It poses a so-called "eradicate-in-place" measure against the virus. Antiviral polysaccharides also provide a green chemistry pathway to virus eradication since these molecules are primarily of biological origin and can be modified by minimal synthetic approaches. They are biocompatible as well as biodegradable. This surface passivation approach could provide a powerful measure against the spreading of coronaviruses.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Polissacarídeos/uso terapêutico , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/metabolismo , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/uso terapêutico , Química Verde , Humanos , Nanopartículas , Nanotecnologia , Polissacarídeos/farmacologia
15.
Nat Commun ; 11(1): 4117, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807785

RESUMO

Strategies for eradicating cancer stem cells (CSCs) are urgently required because CSCs are resistant to anticancer drugs and cause treatment failure, relapse and metastasis. Here, we show that photoactive functional nanocarbon complexes exhibit unique characteristics, such as homogeneous particle morphology, high water dispersibility, powerful photothermal conversion, rapid photoresponsivity and excellent photothermal stability. In addition, the present biologically permeable second near-infrared (NIR-II) light-induced nanocomplexes photo-thermally trigger calcium influx into target cells overexpressing the transient receptor potential vanilloid family type 2 (TRPV2). This combination of nanomaterial design and genetic engineering effectively eliminates cancer cells and suppresses stemness of cancer cells in vitro and in vivo. Finally, in molecular analyses of mechanisms, we show that inhibition of cancer stemness involves calcium-mediated dysregulation of the Wnt/ß-catenin signalling pathway. The present technological concept may lead to innovative therapies to address the global issue of refractory cancers.


Assuntos
Raios Infravermelhos , Nanotecnologia/métodos , Células-Tronco Neoplásicas/efeitos da radiação , Animais , Apoptose/efeitos da radiação , Western Blotting , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Linhagem Celular Tumoral , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Canais de Cátion TRPV/metabolismo , Via de Sinalização Wnt
16.
Biosens Bioelectron ; 167: 112479, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32763826

RESUMO

COVID-19 pandemic outbreak is the most astounding scene ever experienced in the 21st century. It has been determined to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the global pandemic, the lack of efficient rapid and accurate molecular diagnostic testing tools has hindered the public opportunely response to the emerging viral threat. Herein, a DNA nanoscaffold hybrid chain reaction (DNHCR)-based nucleic acid assay strategy is reported for rapid detection of SARS-CoV-2 RNA. In this method, the DNA nanoscaffolds have been first constructed by the self-assembly of long DNA strands and self-quenching probes (H1). Then, the SARS-CoV-2 RNA will initiate the hybridization of H1 and free H2 DNA probes along the nanoscaffold, and an illuminated DNA nanostring is instantly obtained. By taking advantages of the localization design of the H1 probes and the temperature tolerance of the isothermal amplification, the proposed DNHCR method can detect target at short responding time (within 10 min) and mild condition (15 °C-35 °C). Moreover, the reliability of DNHCR method in serum and saliva samples have also been validated. Therefore, DNHCR-based method is expected to provide a simple and faster alternative to the traditional SARS-CoV-2 qRT-PCR assay.


Assuntos
Betacoronavirus , Técnicas Biossensoriais/métodos , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , DNA/síntese química , DNA/química , DNA/genética , Estudos de Viabilidade , Humanos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/estatística & dados numéricos , Nanoestruturas/química , Nanotecnologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Pandemias , Pneumonia Viral/epidemiologia , RNA Viral/análise , RNA Viral/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Nat Commun ; 11(1): 3903, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764543

RESUMO

Top-down mass spectrometry (MS)-based proteomics provides a comprehensive analysis of proteoforms to achieve a proteome-wide understanding of protein functions. However, the MS detection of low-abundance proteins from blood remains an unsolved challenge due to the extraordinary dynamic range of the blood proteome. Here, we develop an integrated nanoproteomics method coupling peptide-functionalized superparamagnetic nanoparticles (NPs) with top-down MS for the enrichment and comprehensive analysis of cardiac troponin I (cTnI), a gold-standard cardiac biomarker, directly from serum. These NPs enable the sensitive enrichment of cTnI (<1 ng/mL) with high specificity and reproducibility, while simultaneously depleting highly abundant proteins such as human serum albumin (>1010 more abundant than cTnI). We demonstrate that top-down nanoproteomics can provide high-resolution proteoform-resolved molecular fingerprints of diverse cTnI proteoforms to establish proteoform-pathophysiology relationships. This scalable and reproducible antibody-free strategy can generally enable the proteoform-resolved analysis of low-abundance proteins directly from serum to reveal previously unachievable molecular details.


Assuntos
Análise Química do Sangue/métodos , Proteínas Sanguíneas/análise , Espectrometria de Massas/métodos , Proteômica/métodos , Troponina I/sangue , Biomarcadores/sangue , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Nanotecnologia , Processamento de Proteína Pós-Traducional , Proteoma/análise , Reprodutibilidade dos Testes , Albumina Sérica Humana/análise
18.
J Infect Public Health ; 13(9): 1243-1246, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32798183

RESUMO

The outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is thought to have occurred first in Wuhan, China in December 2019, before spreading to over 120 countries in the months that followed. It was declared a "public health emergency of international concern" by the World Health Organization on January 31, 2020 and recognized as a pandemic on March 11, 2020. The primary route of SARS-CoV-2 transmission from human to human is through inhalation of respiratory droplets. Devising protective technologies for stopping the spread of the droplets of aerosol containing the viral particles is a vital requirement to curb the ongoing outbreak. However, the current generations of protective respirator masks in use are noted for their imperfect design and there is a need to develop their more advanced analogues, with higher blockage efficiency and the ability to deactivate the trapped bacteria and viruses. It is likely that one such design will be inspired by nanotechnologies. Here we describe a new design from Egypt, utilizing a reusable, recyclable, customizable, antimicrobial and antiviral respirator facial mask feasible for mass production. The novel design is based on the filtration system composed of a nanofibrous matrix of polylactic acid and cellulose acetate containing copper oxide nanoparticles and graphene oxide nanosheets and produced using the electrospinning technique. Simultaneously, the flat pattern fabricated from a thermoplastic composite material is used to provide a solid fit with the facial anatomy. This design illustrates an effort made in a developing setting to provide innovative solutions for combating the SARS-CoV-2 pandemic of potentially global significance.


Assuntos
Cobre , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Máscaras , Doenças Profissionais/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Betacoronavirus , Celulose/análogos & derivados , Egito , Desenho de Equipamento , Grafite , Humanos , Nanopartículas Metálicas , Nanotecnologia , Poliésteres
19.
AAPS PharmSciTech ; 21(6): 226, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32761293

RESUMO

Approximately 40% of compounds in clinical drug development suffer from solubility and bioavailability challenges. Evidence from literature demonstrates the growing interest to utilize flavonoids as potential compounds owing to their widespread therapeutic utility in various ailments. Nobiletin (NOB), one such dietary polymethoxylated flavonoid found in citrus fruits, has multiple pharmacological effects such as antioxidant, anti-microbial, anti-cancer, and anti-inflammatory. It is useful in cancer, inflammatory bowel diseases, atherosclerosis, obesity, and Alzheimer's disease. Although preclinical studies demonstrate the therapeutic utility of NOB, it suffers from serious biopharmaceutical limitations such as low aqueous solubility (below 1 µg/ml), poor permeability across biological barriers, and low bioavailability. To overcome these biopharmaceutical challenges associated with NOB, the use of advanced formulations and nanotechnology-based strategies appears to be a promising approach to potentiate its therapeutic action. Multiple reviews cover the various therapeutic benefits of NOB in various diseases; however, there is an absence of a comprehensive review that focuses on the formulation development strategies of NOB. The purpose of this review is to provide a concise perspective on NOB as a candidate molecule for formulation development. The manuscript covers various aspects related to NOB, such as its chemistry, physicochemical properties, and pharmacological effects. This is also a thorough review of various formulation development strategies with advances made in the past years to improve the solubility, bioavailability, and therapeutic efficacy of NOB. The review also contains information related to toxicity and patents involving NOB and its formulation.


Assuntos
Antioxidantes/química , Composição de Medicamentos , Flavonas/química , Nanotecnologia , Animais , Antioxidantes/farmacocinética , Disponibilidade Biológica , Flavonas/farmacocinética , Humanos , Solubilidade
20.
Proc Natl Acad Sci U S A ; 117(35): 21403-21412, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32817418

RESUMO

The early steps of DNA double-strand break (DSB) repair in human cells involve the MRE11-RAD50-NBS1 (MRN) complex and its cofactor, phosphorylated CtIP. The roles of these proteins in nucleolytic DSB resection are well characterized, but their role in bridging the DNA ends for efficient and correct repair is much less explored. Here we study the binding of phosphorylated CtIP, which promotes the endonuclease activity of MRN, to single long (∼50 kb) DNA molecules using nanofluidic channels and compare it to the yeast homolog Sae2. CtIP bridges DNA in a manner that depends on the oligomeric state of the protein, and truncated mutants demonstrate that the bridging depends on CtIP regions distinct from those that stimulate the nuclease activity of MRN. Sae2 is a much smaller protein than CtIP, and its bridging is significantly less efficient. Our results demonstrate that the nuclease cofactor and structural functions of CtIP may depend on the same protein population, which may be crucial for CtIP functions in both homologous recombination and microhomology-mediated end-joining.


Assuntos
Quebras de DNA de Cadeia Dupla , DNA Circular/metabolismo , Endodesoxirribonucleases/metabolismo , Animais , Endonucleases/metabolismo , Humanos , Nanotecnologia , Fosforilação , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomycetales , Células Sf9 , Spodoptera
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