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1.
Arch Virol ; 169(9): 190, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39222118

RESUMO

Mitoviruses are cryptic capsidless viruses belonging to the family Mitoviridae that replicate and are maintained in the mitochondria of fungi. Complete mitovirus-like sequences were recently assembled from plant transcriptome data and plant leaf tissue samples. Passion fruit (Passiflora spp.) is an economically important crop for numerous tropical and subtropical countries worldwide, and many virus-induced diseases impact its production. From a large-scale genomic study targeting viruses infecting Passiflora spp. in Brazil, we detected a de novo-assembled contig with similarity to other plant-associated mitoviruses. The contig is ∼2.6 kb long, with a single open reading frame (ORF) encoding an RNA-dependent RNA polymerase (RdRP). This contig has been named "passion fruit mitovirus-like 1" (PfMv1). An alignment of the predicted amino acid sequence of the RdRP of PfMv1 and those of other plant-associated mitoviruses revealed the presence of the six conserved motifs of mitovirus RdRPs. PfMv1 has 79% coverage and 50.14% identity to Humulus lupulus mitovirus 1. Phylogenetic analysis showed that PfMV1 clustered with other plant-associated mitoviruses in the genus Duamitovirus. Using RT-PCR, we detected a PfMv1-derived fragment, but no corresponding DNA was identified, thus excluding the possibility that this is an endogenized viral-like sequence. This is the first evidence of a replicating mitovirus associated with Passiflora edulis, and it should be classified as a member of a new species, for which we propose the name "Duamitovirus passiflorae".


Assuntos
Genoma Viral , Fases de Leitura Aberta , Passiflora , Filogenia , Doenças das Plantas , RNA Polimerase Dependente de RNA , Passiflora/virologia , Genoma Viral/genética , Doenças das Plantas/virologia , Brasil , RNA Polimerase Dependente de RNA/genética , Vírus de RNA/genética , Vírus de RNA/isolamento & purificação , Vírus de RNA/classificação , Proteínas Virais/genética , RNA Viral/genética , Sequência de Aminoácidos
2.
An Acad Bras Cienc ; 96(suppl 1): e20240234, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39258701

RESUMO

Jacobsite is a relatively rare mineral of composition MnFe2O4, found in Urandi (Bahia State) in Brazil. It is also a common species in the deep-sea manganese nodules, attracting the interest of many mineral-extracting companies. Because of its spinel constitution similar to magnetite, Jacobsite is commonly called a manganese-ferrite. However, the manganese/iron content may vary substantially according to its origin, demanding specific studies in each case. The Jacobsite mineral inspired our laboratory synthesis of the analogous manganese ferrite nanoparticles. The direct synthesis by the coprecipitation method has not been successful; however, it can be carried in the presence of citrate ions, yielding strongly magnetic nanoparticles, with a maximum magnetization of 45.6 emu.g1. Although they were structurally identical to Jacobsite, the mineral from Bahia exhibited a rather weak magnetism, because it involves a ferrimagnetic coupling. For this reason, the synthetic method seems to provide a better way of obtaining strongly magnetic manganese ferrites. These magnetic nanoparticles have been investigated in detail, including their interaction with diatoms, providing interesting magnetic bio-silicate carriers in drug delivery.


Assuntos
Compostos Férricos , Compostos de Manganês , Compostos de Manganês/química , Compostos Férricos/química , Nanopartículas/química , Manganês/química , Brasil , Minerais/química
3.
Phys Rev Lett ; 133(6): 060401, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39178447

RESUMO

With the control of increasingly complex quantum systems, the relevant degrees of freedom we are interested in may not be those traditionally addressed by statistical quantum mechanics. Here, we employ quantum channels to define generalized subsystems, capturing the pertinent degrees of freedom, and obtain their associated canonical state. We show that the generalized subsystem description from almost any microscopic pure state of the whole system will behave similarly to its corresponding canonical state. Such canonical typicality behavior depends on the entropy of the channel used to define the generalized subsystem.

4.
Membranes (Basel) ; 14(4)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38668112

RESUMO

The human Respiratory Syncytial Virus (hRSV) stands as one of the most common causes of acute respiratory diseases. The infectivity of this virus is intricately linked to its membrane proteins, notably the attachment glycoprotein (G protein). The latter plays a key role in facilitating the attachment of hRSV to respiratory tract epithelial cells, thereby initiating the infection process. The present study aimed to characterize the interaction of the conserved cysteine-noose domain of hRSV G protein (cndG) with the transmembrane CX3C motif chemokine receptor 1 (CX3CR1) isoforms using computational tools of molecular modeling, docking, molecular dynamics simulations, and binding free energy calculations. From MD simulations of the molecular system embedded in the POPC lipid bilayer, we showed a stable interaction of cndG with the canonical fractalkine binding site in the N-terminal cavity of the CX3CR1 isoforms and identified that residues in the extracellular loop 2 (ECL2) region and Glu279 of this receptor are pivotal for the stabilization of CX3CR1/cndG binding, corroborating what was reported for the interaction of the chemokine fractalkine with CX3CR1 and its structure homolog US28. Therefore, the results presented here contribute by revealing key structural points for the CX3CR1/G interaction, allowing us to better understand the biology of hRSV from its attachment process and to develop new strategies to combat it.

5.
Int J Biol Macromol ; 259(Pt 2): 129192, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38216013

RESUMO

Old Yellow Enzymes (OYEs) are flavin-dependent redox enzymes that promote the asymmetric reduction of activated alkenes. Due to the high importance of flavoenzymes in the metabolism of organisms, the interaction between OYEs from the parasites Trypanosoma cruzi and Leishmania braziliensis and three diterpene icetexanes (brussonol and two analogs), were evaluated in the present study, and differences in the binding mechanism and inhibition capacity of these molecules were examined. Although the aforementioned compounds showed poor and negligible activities against T. cruzi and L. braziliensis cells, respectively, the experiments with the purified enzymes indicated that the interaction occurs by divergent mechanisms. Overall, the ligands' inhibitory effect depends on their accessibility to the N5 position of the flavin's isoalloxazine ring. The results also indicated that the OYEs found in both parasites share structural similarities and showed affinities for the diterpene icetexanes in the same range. Nevertheless, the interaction between OYEs and ligands is directed by enthalpy and/or entropy in distinct ways. In conclusion, the binding site of both OYEs exhibits remarkable plasticity, and a large range of different molecules, including that can be substrates and inhibitors, can bind this site. This plasticity should be considered in drug design using OYE as a target.


Assuntos
Doença de Chagas , Leishmania braziliensis , Trypanosoma cruzi , Humanos , NADPH Desidrogenase/química , NADPH Desidrogenase/farmacologia , Doença de Chagas/parasitologia , Flavinas/farmacologia
6.
Folia Microbiol (Praha) ; 69(1): 91-99, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38017300

RESUMO

Bacillus thuringiensis (Bt) is known for its Cry and Vip3A pesticidal proteins with high selectivity to target pests. Here, we assessed the potential of a novel neotropical Bt strain (UFT038) against six lepidopteran pests, including two Cry-resistant populations of fall armyworm, Spodoptera frugiperda. We also sequenced and analyzed the genome of Bt UFT038 to identify genes involved in insecticidal activities or encoding other virulence factors. In toxicological bioassays, Bt UFT038 killed and inhibited the neonate growth in a concentration-dependent manner. Bt UFT038 and HD-1 were equally toxic against S. cosmioides, S. frugiperda (S_Bt and R_Cry1 + 2Ab populations), Helicoverpa zea, and H. armigera. However, larval growth inhibition results indicated that Bt UFT038 was more toxic than HD-1 to S. cosmioides, while HD-1 was more active against Chrysodeixis includens. The draft genome of Bt UFT038 showed the cry1Aa8, cry1Ac11, cry1Ia44, cry2Aa9, cry2Ab35, and vip3Af5 genes. Besides this, genes encoding the virulence factors (inhA, plcA, piplC, sph, and chi1-2) and toxins (alo, cytK, hlyIII, hblA-D, and nheA-C) were also identified. Collectively, our findings reveal the potential of the Bt UFT038 strain as a source of insecticidal genes against lepidopteran pests, including S. cosmioides and S. frugiperda.


Assuntos
Bacillus thuringiensis , Inseticidas , Mariposas , Animais , Humanos , Recém-Nascido , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Glycine max , Endotoxinas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Proteínas Hemolisinas/farmacologia , Inseticidas/farmacologia , Inseticidas/metabolismo , Spodoptera/metabolismo , Larva , Fatores de Virulência/metabolismo , Controle Biológico de Vetores
7.
Arch Virol ; 168(12): 286, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37940763

RESUMO

The discovery rate of new plant viruses has increased due to studies involving high-throughput sequencing (HTS), particularly for single-stranded DNA viruses of the family Genomoviridae. We carried out an HTS-based survey of genomoviruses in a wide range of native and exotic trees grown in the Brazilian Cerrado biome, and the complete genome sequences of two novel members of the family Genomoviridae from two distinct genera were determined. Specific primers were designed to detect these genomoviruses in individual samples. A new gemykolovirus (Tecoma stans associated gemykolovirus) was detected in Tecoma stans, and a new gemykibivirus (Ouratea duparquetiana associated gemykibivirus) was detected in Ouratea duparquetiana. A gemykrogvirus related to Gila monster associated gemykrogvirus (80% pairwise identity) was also detected in foliar samples of Trembleya parviflora. Our pilot study paves the way for a better characterization of this diverse collection of genomoviruses as well as their interactions with the associated tree species.


Assuntos
Vírus de DNA , Plantas , Vírus de DNA/genética , Brasil , Projetos Piloto , Filogenia , Ecossistema , Árvores
8.
J Chem Inf Model ; 63(20): 6344-6353, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37824286

RESUMO

The folding process of multidomain proteins is a highly intricate phenomenon involving the assembly of distinct domains into a functional three-dimensional structure. During this process, each domain may fold independently while interacting with others. The folding of multidomain proteins can be influenced by various factors, including their composition, the structure of each domain, or the presence of disordered regions, as well as the surrounding environment. Misfolding of multidomain proteins can lead to the formation of nonfunctional structures associated with a range of diseases, including cancers or neurodegenerative disorders. Understanding this process is an important step for many biophysical analyses such as stability, interaction, malfunctioning, and rational drug design. One such multidomain protein is growth factor receptor-bound protein 2 (GRB2), an adaptor protein that is essential in regulating cell survival. GRB2 consists of one central Src homology 2 (SH2) domain flanked by two Src homology 3 (SH3) domains. The SH2 domain interacts with phosphotyrosine regions in other proteins, while the SH3 domains recognize proline-rich regions on protein partners during cell signaling. Here, we combined computational and experimental techniques to investigate the folding process of GRB2. Through computational simulations, we sampled the conformational space and mapped the mechanisms involved by the free energy profiles, which may indicate possible intermediate states. From the molecular dynamics trajectories, we used the energy landscape visualization method (ELViM), which allowed us to visualize a three-dimensional (3D) representation of the overall energy surface. We identified two possible parallel folding routes that cannot be seen in a one-dimensional analysis, with one occurring more frequently during folding. Supporting these results, we used differential scanning calorimetry (DSC) and fluorescence spectroscopy techniques to confirm these intermediate states in vitro. Finally, we analyzed the deletion of domains to compare our model outputs to previously published results, supporting the presence of interdomain modulation. Overall, our study highlights the significance of interdomain communication within the GRB2 protein and its impact on the formation, stability, and structural plasticity of the protein, which are crucial for its interaction with other proteins in key signaling pathways.


Assuntos
Neoplasias , Transdução de Sinais , Sequência de Aminoácidos , Proteína Adaptadora GRB2 , Fosfotirosina , Ligação Proteica , Domínios de Homologia de src
9.
Rev. argent. reumatolg. (En línea) ; 34(2): 69-72, oct. 2023. graf
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1521648

RESUMO

Resumen Los síndromes esclerodermiformes suelen imitar muy bien una esclerosis sistémica progresiva, y es la presencia de ampollas cutáneas en áreas fotoexpuestas con hiperpigmentación los datos diferenciales para diagnosticar una porfiria. Presentamos el caso de un varón de 48 años con fotosensibilidad, fragilidad capilar, ampollas cutáneas e hiperpigmentación asociado a esclerodactilia, con pérdida cicatrizal distal de tejido en los dedos de las manos, que simuló a la perfección una esclerosis sistémica progresiva. La analítica mostró negatividad para anticuerpos antinucleares, antitopoisomerasa y anticentrómero, con valores altos de uroporfirinas en orina. El tratamiento con flebotomías e hidroxicloquina mejoró la fotosensibilidad y la fragilidad cutánea.


Abstract Sclerodermiform syndromes usually mimic progressive systemic sclerosis very well, with the presence of skin blisters in photo-exposed areas with hyperpigmentation being the differential data for diagnosing porphyria. We present the case of a 48-year old man with photosensitivity, capillary fragility, skin blisters, and hyperpigmentation associated with sclerodactyly with distal scar tissue loss on the fingers, which perfectly simulated progressive systemic sclerosis. The analysis showed negativity for antinuclear, antitopoisomerase and anticentromere antibodies, with high levels of uroporphyrins in urine. Phlebotomy and hydroxycloquine treatment improved photosensitivity and skin fragility.


Assuntos
Porfiria Cutânea Tardia , Escleroderma Sistêmico , Uroporfirinas
10.
Methods Mol Biol ; 2705: 135-151, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37668973

RESUMO

Protein interactions are at the essence of life. Proteins evolved not to have stable structures, but rather to be specialized in participating in a network of interactions. Every interaction involving proteins comprises the formation of an encounter complex, which may have two outcomes: (i) the dissociation or (ii) the formation of the final specific complex. Here, we present a methodology to characterize the encounter complex of the Grb2-SH2 domain with a phosphopeptide. This method can be generalized to other protein partners. It consists of the measurement of 15N CPMG relaxation dispersion (RD) profiles of the protein in the free state, which describes the residues that are in conformational exchange. We then acquire the dispersion profiles of the protein at a semisaturated concentration of the ligand. At this condition, the chemical exchange between the free and bound state leads to the observation of dispersion profiles in residues that are not in conformational exchange in the free state. This is due to fuzzy interactions that are typical of the encounter complexes. The transient "touching" of the ligand in the protein partner generates these new relaxation dispersion profiles. For the Grb2-SH2 domain, we observed a wider surface at SH2 for the encounter complex than the phosphopeptide (pY) binding site, which might explain the molecular recognition of remote phosphotyrosine. The Grb2-SH2-pY encounter complex is dominated by electrostatic interactions, which contribute to the fuzziness of the complex, but also have contribution of hydrophobic interactions.


Assuntos
Fosfopeptídeos , Domínios de Homologia de src , Ligantes , Imageamento por Ressonância Magnética , Sítios de Ligação
11.
Trop Plant Pathol ; : 1-9, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37362078

RESUMO

Frequent monitoring of emerging viruses of agricultural crops is one of the most important missions for plant virologists. A fast and precise identification of potential harmful viruses may prevent the occurrence of serious epidemics. Nowadays, high-throughput sequencing (HTS) technologies became an accessible and powerful tool for this purpose. The major discussion of this strategy resides in the process of sample collection, which is usually laborious, costly and nonrepresentative. In this study, we assessed the use of sewage water samples for monitoring the widespread, numerous, and stable plant viruses using HTS analysis and RT-qPCR. Plant viruses belonged to 12 virus families were found, from which Virgaviridae, Solemoviridae, Tymoviridae, Alphaflexiviridae, Betaflexiviridae, Closteroviridae and Secoviridae were the most abundant ones with more than 20 species. Additionally, we detected one quarantine virus in Brazil and a new tobamovirus species. To assess the importance of the processed foods as virus release origins to sewage, we selected two viruses, the tobamovirus pepper mild mottle virus (PMMoV) and the carlavirus garlic common latent virus (GarCLV), to detect in processed food materials by RT-qPCR. PMMoV was detected in large amount in pepper-based processed foods and in sewage samples, while GarCLV was less frequent in dried and fresh garlic samples, and in the sewage samples. This suggested a high correlation of virus abundance in sewage and processed food sources. The potential use of sewage for a virus survey is discussed in this study. Supplementary Information: The online version contains supplementary material available at 10.1007/s40858-023-00575-8.

12.
An. Fac. Med. (Perú) ; 84(2)jun. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1447191

RESUMO

Tanto lupus eritematoso sistémico como el síndrome antifosfolípido son enfermedades autoinmunes con potencial tromboembólico, sobre todo por la presencia de anticuerpos trombogénicos. El pulmón es un lugar común donde suele asentarse un trombo y generar una tromboembolia, a veces con posterior infarto y cavitación. Existen pocos estudios que informen un infarto pulmonar cavitado en un paciente con lupus asociado a síndrome antifosfolípido. Presentamos el caso de una mujer de 24 años con síntomas generales y lesión pulmonar derecha cavitada. Fue tratada inicialmente como infección tuberculosa o fúngica. La analítica y las imágenes orientaron y diagnosticaron lupus asociado a síndrome antifosfolípido, complicado con tromboembolismo pulmonar que luego pasó a cavitarse. La paciente mejoró considerablemente con anticoagulantes, corticoides y ciclofosfamida.


Both systemic lupus erythematosus and antiphospholipid syndrome are autoimmune diseases with thromboembolic potential, especially due to the presence of thrombogenic antibodies. The lung is a common place where a thrombus usually settles and generates a thromboembolism, sometimes with subsequent infarction and cavitation. There are few studies reporting cavitary pulmonary infarction in a patient with lupus associated with antiphospholipid syndrome. We present the case of a 24-year-old woman with general symptoms and cavitated right lung lesion. She was initially treated as tuberculous or fungal infection. Laboratory tests and images guided and diagnosed lupus associated with antiphospholipid syndrome, complicated by pulmonary thromboembolism that later became cavitated. The patient improved considerably with anticoagulants, corticosteroids, and cyclophosphamide.

13.
Viruses ; 15(2)2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36851624

RESUMO

High-throughput sequencing (HTS) has been an important tool for the discovery of plant viruses and their surveillance. In 2015, several virus-like symptoms were observed in passion fruit (PF) plants in Bahia state, Brazil. Using HTS technology, bioinformatics tools, RT-PCR, and Sanger sequencing, we identified the cucurbit aphid-borne yellows virus (CABYV, Polerovirus, Solemoviridae) in co-infection with cowpea aphid-borne mosaic virus (CABMV, Potyvirus, Potyviridae) in PF, in green manure, and spontaneous plants in several localities in Bahia. Complete genomes of CABYV-PF isolates were determined and analyzed with other CABYV isolates available in GenBank that have been identified in various countries. Phylogenetic analysis and pairwise identity comparison with CABYV isolates showed that CABYV-PFs are more closely related to French and Spanish isolates. Overall, analyses of all the CABYV genomes revealed that these could represent ten distinct species, and we thus proposed reclassifying these CABYV as isolates into ten species, tentatively named "Polerovirus curcubitaeprimum" to "Polerovirus curcubitaenonum", and "Polerovirus melo". CABYV-PF is a member of "Polerovirus curcubitaeprimum".


Assuntos
Luteoviridae , Passiflora , Brasil , Frutas , Filogenia , Luteoviridae/genética
14.
Biophys Chem ; 295: 106973, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36827855

RESUMO

Cancer cells present an increased replicative potential as a hallmark. The increased replication leads to a higher intracellular pH. Grb2, an adapter protein, is mainly involved in several types of cancers due to its role in signaling pathways responsible for cell growth and proliferation. At pH 7, we observed a more compact structure, as seen by DLS and 1H NMR relaxation experiments, with high cooperativity within domains. On the other hand, we observed an increase in disordered structures at pH 8, with relative independence between domains characterized by higher melting temperatures and enthalpy of unfolding. CD and DLS corroborate with these observations at pH 8, conferring more flexibility among the domains, followed by lower unfolding cooperativity and increased hydrodynamic diameter at higher pH. In addition, 15N-HSQC chemical shift perturbations experiments showed significant differences in the positions of several amino acids spread on the Grb2 structure when pH was changed, which agrees with the previous results. Finally, the molecular dynamic analysis demonstrates that Grb2 presents a movement pattern where both SH3 domains move toward the center of the protein at pH 7. On the contrary, the pattern changes its direction at pH 8, where domains move outside the center of the protein, conferring a more elongated structure at higher pH. So, Grb2 presents significant structural and dynamic changes modulated by pH. If considering the role of Grb2 in cell signaling upstream, these conformational changes could be a critical mechanistic behavior of this protein, preventing/disrupting the stability of the cell signaling pathways related to cancer.


Assuntos
Simulação de Dinâmica Molecular , Transdução de Sinais , Proteína Adaptadora GRB2/química , Espectroscopia de Ressonância Magnética , Concentração de Íons de Hidrogênio , Domínios de Homologia de src , Ligação Proteica
15.
J Gen Virol ; 103(11)2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36399124

RESUMO

Currently, many viruses are classified based on their genome organization and nucleotide/amino acid sequence identities of their capsid and replication-associated proteins. Although biological traits such as vector specificities and host range are also considered, this later information is scarce for the majority of recently identified viruses, characterized only from genomic sequences. Accordingly, genomic sequences and derived information are being frequently used as the major, if not only, criteria for virus classification and this calls for a full review of the process. Herein, we critically addressed current issues concerning classification of viruses in the family Betaflexiviridae in the era of high-throughput sequencing and propose an updated set of demarcation criteria based on a process involving pairwise identity analyses and phylogenetics. The proposed framework has been designed to solve the majority of current conundrums in taxonomy and to facilitate future virus classification. Finally, the analyses performed herein, alongside the proposed approaches, could be used as a blueprint for virus classification at-large.


Assuntos
Flexiviridae , Vírus , Flexiviridae/genética , Genoma Viral , Vírus/genética , Filogenia , Sequenciamento de Nucleotídeos em Larga Escala
16.
Viruses ; 14(10)2022 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-36298869

RESUMO

BACKGROUND: The correct understanding of the epidemiological dynamics of COVID-19, caused by the SARS-CoV-2, is essential for formulating public policies of disease containment. METHODS: In this study, we constructed a picture of the epidemiological dynamics of COVID-19 in a Brazilian population of almost 17000 patients in 15 months. We specifically studied the fluctuations of COVID-19 cases and deaths due to COVID-19 over time according to host gender, age, viral load, and genetic variants. RESULTS: As the main results, we observed that the numbers of COVID-19 cases and deaths due to COVID-19 fluctuated over time and that men were the most affected by deaths, as well as those of 60 or more years old. We also observed that individuals between 30- and 44-years old were the most affected by COVID-19 cases. In addition, the viral loads in the patients' nasopharynx were higher in the early symptomatic period. We found that early pandemic SARS-CoV-2 lineages were replaced by the variant of concern (VOC) P.1 (Gamma) in the second half of the study period, which led to a significant increase in the number of deaths. CONCLUSIONS: The results presented in this study are helpful for future formulations of efficient public policies of COVID-19 containment.


Assuntos
COVID-19 , SARS-CoV-2 , Masculino , Humanos , Pessoa de Meia-Idade , Adulto , SARS-CoV-2/genética , Pandemias , Brasil/epidemiologia , COVID-19/epidemiologia , Nasofaringe
17.
Nanomaterials (Basel) ; 12(18)2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36144933

RESUMO

Inflammasomes are cytosolic complexes composed of a Nod-like receptor, NLR, the adaptor protein, ASC, and a proteolytic enzyme, caspase-1. Inflammasome activation leads to caspase-1 activation and promotes functional maturation of IL-1ß and IL-18, two prototypical inflammatory cytokines. Besides, inflammasome activation leads to pyroptosis, an inflammatory type of cell death. Inflammasomes are vital for the host to cope with foreign pathogens or tissue damage. Herein, we show that quantum-dot-based iron oxide nanoparticles, MNP@QD, trigger NLRP3 inflammasome activation and subsequent release of proinflammatory interleukin IL-1ß by murine bone marrow-derived dendritic cells (BMDCs). This activation is more pronounced if these cells endocytose the nanoparticles before receiving inflammatory stimulation. MNP@QD was characterized by using imaging techniques like transmission electron microscopy, fluorescence microscopy, and atomic force microscopy, as well as physical and spectroscopical techniques such as fluorescence spectroscopy and powder diffraction. These findings may open the possibility of using the composite MNP@QD as both an imaging and a therapeutic tool.

18.
An Acad Bras Cienc ; 94(3): e20210917, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35920489

RESUMO

Molecular machines, as exemplified by the kinesin and microtubule system, are responsible for molecular transport in cells. The monitoring of the cellular machinery has attracted much attention in recent years, requiring sophisticated techniques such as optical tweezers, and dark field hyperspectral and fluorescence microscopies. It also demands suitable procedures for immobilization and labeling with functional agents such as dyes, plasmonic nanoparticles and quantum dots. In this work, microtubules were co-polymerized by incubating a tubulin mix consisting of 7 biotinylated tubulin to 3 rhodamine tubulin. Rhodamine provided the fluorescent tag, while biotin was the anchoring group for receiving streptavidin containing species. To control the microtubule alignment and consequently, the molecular gliding directions, functionalized iron oxide nanoparticles were employed in the presence of an external magnet field. Such iron oxide nanoparticles, (MagNPs) were previously coated with silica and (3-aminopro-pyl)triethoxysilane (APTS) and then modified with streptavidin (SA) for linking to the biotin-functionalized microtubules. In this way, the binding has been successfully performed, and the magnetic alignment probed by Inverted Fluorescence Microscopy. The proposed strategy has proved promising, as tested with one of the most important biological structures of the cellular machinery.


Assuntos
Biotina , Tubulina (Proteína) , Biotina/análise , Biotina/química , Biotina/metabolismo , Óxido Ferroso-Férrico/análise , Óxido Ferroso-Férrico/metabolismo , Fenômenos Magnéticos , Microscopia de Fluorescência , Microtúbulos/química , Microtúbulos/metabolismo , Rodaminas/análise , Rodaminas/metabolismo , Estreptavidina/análise , Estreptavidina/química , Estreptavidina/metabolismo , Tubulina (Proteína)/análise , Tubulina (Proteína)/metabolismo
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 283: 121751, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-35973382

RESUMO

Human respiratory syncytial virus (hRSV) infections are one of the most causes of acute lower respiratory tract infections in children and elderly. The development of effective antiviral therapies or preventive vaccines against hRSV is not available yet. Thus, it is necessary to search for protein targets to combat this viral infection, as well as potential ways to block them. Non-Structural 1 (NS1) protein is an important factor for viral replication success since reduces the immune response by interacting with proteins in the type I interferon pathway. The influence of NS1 on the cell's immune response denotes the potential of its inhibition, being a possible target of treatment against hRSV infection. Here, it was studied the interaction of hRSV NS1 with natural flavonoids chrysin, morin, kaempferol, and myricetin and their mono-acetylated chrysin and penta-acetylated morin derivatives using spectroscopic techniques and computational simulations. The fluorescence data indicate that the binding affinities are on the order of 105 M-1, which are directly related to the partition coefficient of each flavonoid with Pearson's correlation coefficients of 0.76-0.80. The thermodynamic analysis suggests that hydrophobic interactions play a key role in the formation of the NS1/flavonoid complexes, with positive values of enthalpy and entropy changes. The computational approach proposes that flavonoids bind in a region of NS1 formed between the C-terminal α3-helix and the protein core, important for its biological function, and corroborate with experimental data revealing that hydrophobic contacts are important for the binding. Therefore, the present study provides relevant molecular details for the development of a possible new strategy to fight infections caused by hRSV.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Idoso , Criança , Flavonoides/farmacologia , Humanos , Vírus Sincicial Respiratório Humano/química , Vírus Sincicial Respiratório Humano/fisiologia , Termodinâmica
20.
Life (Basel) ; 12(5)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35629324

RESUMO

Photobiomodulation therapy (PBMT) has been used to treat patients with chronic neck and/or shoulder pain. However, it is unknown whether the concurrent use of PBMT and static magnetic field (PBMT-sMF) also has positive effects in these patients. The aim of this study was to investigate the effects of PBMT-sMF versus placebo on pain intensity, range of motion (ROM) and treatment satisfaction in patients with chronic nonspecific neck and/or shoulder pain. A randomized controlled trial, with blinded assessors, therapists and patients was carried out. Seventy-two patients with chronic nonspecific neck and/or shoulder pain were randomized to either active PBMT-sMF (n = 36) or placebo PBMT-sMF (n = 36). Patients were treated twice weekly, over 3 weeks. Primary outcome was pain intensity, measured 15 min after the last treatment session and at 24-, 48-, 72-h, and 7-days after the last treatment. Secondary outcomes were ROM, patient' treatment satisfaction, and adverse effects. PBMT-sMF was able to reduce pain intensity in all time points tested compared to placebo (p < 0.05). There was no difference between groups in the secondary outcomes (p > 0.05). Our results suggest that PBMT-sMF is better than placebo to reduce pain in patients with chronic nonspecific neck and/or shoulder pain at short-term.

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