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1.
Int J Mol Sci ; 25(18)2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39337556

RESUMO

Alzheimer's disease (AD) is one of the most common causes of dementia, accounting for more than 60% of all cases. It is a neurodegenerative disease in which symptoms such as a decline in memory, thinking, learning, and organizing skills develop gradually over many years and eventually become more severe. To date, there is no effective treatment for the cause of Alzheimer's disease, and the existing pharmacological options primarily help manage symptoms. Treatment is mainly based on acetylcholinesterase (AChE) inhibitors such as donepezil, rivastigmine, and galantamine, which exhibit numerous adverse cardiovascular and gastrointestinal effects due to excessive stimulation of peripheral cholinergic activity involving muscarinic receptors. Therefore, in addition to the obvious drugs that act on the cause of the disease, new drugs based on AChE inhibition that show the fewest side effects are needed. One potential drug could be a new compound under study, tetrahydroacridine derivative (CHDA), which showed significant potential to inhibit the AChE enzyme in previous in vitro studies. The present study shows that while having very potent AChE inhibitory properties, CHDA is a compound with low toxicity to nerve cell culture and living organisms. In addition, it exhibits dissociative activity against amyloid ß fibrils, which is extremely important for applications in Alzheimer's disease therapy.


Assuntos
Acetilcolinesterase , Peptídeos beta-Amiloides , Inibidores da Colinesterase , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Peptídeos beta-Amiloides/metabolismo , Humanos , Acetilcolinesterase/metabolismo , Acetilcolinesterase/química , Acridinas/farmacologia , Acridinas/química , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Amiloide/metabolismo
2.
Adv Healthc Mater ; : e2402431, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39279434

RESUMO

Bacterial keratitis (BK) is a severe eye infection commonly associated with Staphylococcus aureus (S. aureus), posing a significant risk to vision, especially among contact lens wearers. This research introduces a novel smart nanoplatform (deMS@cNF), developed from demineralized mussel shells (deMS) and reinforced with chitin (CT) nanofibrils, specifically designed for portable photothermal disinfection of contact lenses. The nanoplatform leverages the photothermal properties of eumelanin in mussel shells (MS), which, when activated by a simple bike flashlight, rapidly heats to temperatures up to 95 °C, effectively destroying bacterial contamination. In vitro tests demonstrate that the nanoplatform is biocompatible and non-toxic, making it suitable for medical applications. This study highlights an innovative approach to converting marine biowaste into a safe, effective, and low-cost portable method for disinfecting contact lenses, showcasing the potential of the deMS@cNF platform for broader antimicrobial applications.

3.
Sci Rep ; 14(1): 20822, 2024 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-39242631

RESUMO

A new type of hybrid polymer particles capable of carrying the cytostatic drug doxorubicin and labeled with a gallium compound was prepared. These microparticles consist of a core and a hydrogel shell, which serves as the structural matrix. The shell can be employed to immobilize gallium oxide hydroxide (GaOOH) nanoparticles and the drug, resulting in hybrid beads with sizes of approximately 3.81 ± 0.09 µm. The microparticles exhibit the ability to incorporate a remarkably large amount of doxorubicin, approximately 0.96 mg per 1 mg of the polymeric carrier. Additionally, GaOOH nanoparticles can be deposited within the hydrogel layer at an amount of 0.64 mg per 1 mg of the carrier. These nanoparticles, resembling rice grains with an average size of 593 nm by 155 nm, are located on the surface of the polymer carrier. In vitro studies on breast and colon cancer cell lines revealed a pronounced cytotoxic effect of the hybrid polymer particles loaded with doxorubicin, indicating their potential for cancer therapies. Furthermore, investigations on doping the hybrid particles with the Ga-68 radioisotope demonstrated their potential application in positron emission tomography (PET) imaging. The proposed structures present a promising theranostic platform, where particles could be employed in anticancer therapies while monitoring their accumulation in the body using PET.


Assuntos
Doxorrubicina , Gálio , Hidrogéis , Nanopartículas , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Humanos , Gálio/química , Nanopartículas/química , Hidrogéis/química , Portadores de Fármacos/química , Linhagem Celular Tumoral , Radioisótopos de Gálio/química , Tomografia por Emissão de Pósitrons , Hidróxidos/química , Sobrevivência Celular/efeitos dos fármacos , Tamanho da Partícula
4.
EJNMMI Res ; 14(1): 63, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976101

RESUMO

BACKGROUND: Positron emission tomography (PET) is now an established diagnostic method for myocardial perfusion imaging (MPI) in coronary artery disease, which is the main cause of death globally. The available tracers show several limitations, therefore, the 18F-labelled tracer is in high demand nowadays. The preclinical studies on normal Wistar rats aimed to characterise two potential, novel radiotracers, [18F]SYN1 and [18F]SYN2, to evaluate which is a better candidate for PET MPI cardiotracer. RESULTS: The dynamic microPET images showed rapid myocardial uptake for both tracers. However, the uptake was higher and also stable for [18F]SYN2, with an average standardized uptake value of 3.8. The biodistribution studies confirmed that [18F]SYN2 uptake in the cardiac muscle was high and stable (3.02%ID/g at 15 min and 2.79%ID/g at 6 h) compared to [18F]SYN1 (1.84%ID/g at 15 min and 0.32%ID/g at 6 h). The critical organs determined in dosimetry studies were the small intestine and the kidneys. The estimated effective dose for humans was 0.00714 mSv/MBq for [18F]SYN1 and 0.0109 mSv/MBq for [18F]SYN2. The tested dose level of 2 mg/kg was considered to be the No Observed Adverse Effect Level (NOAEL) for both candidates. The better results were achieved for [18F]SYN2, therefore, further preclinical studies were conducted only for this tracer. Radioligand binding assays showed significant responses in 3 from 68 assays: muscarinic acetylcholine M1 and M2 receptors and potassium channel hERG. The compound was mostly metabolised via an oxidative N-dealkylation, while the fluor substituent was not separated from the molecule. CONCLUSION: [18F]SYN2 showed a favourable pharmacodynamic and pharmacokinetic profile, which enabled a clear visualization of the heart in microPET. The compound was well-tolerated in studies in normal rats with moderate radiation exposure. The results encourage further exploration of [18F]SYN2 in clinical studies.

5.
Sci Rep ; 14(1): 17304, 2024 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-39068177

RESUMO

In contrast to abiotically formed carbonates, biogenetic carbonates have been observed to be nanocomposite, organo-mineral structures, the basic build-blocks of which are particles of quasi-uniform size (10-100 nm) organized into complex higher-order hierarchical structures, typically with highly controlled crystal-axis alignments. Some of these characteristics serve as criteria for inferring a biological origin and the state of preservation of fossil carbonate materials, and to determine whether the biomineralization process was biologically induced or controlled. Here we show that a calcium storage structure formed by the American lobster, a gastrolith initially consisting of amorphous calcium carbonate (ACC) and amorphous calcium phosphate (ACP), post-mortem can crystallize into (thus secondary) calcite with structural properties strongly influenced by the inherited organic matrix. This secondary calcite meets many structural criteria for biominerals (thus called the biomorphic calcite), but differs in trace element distributions (e.g., P and Mg). Such observations refine the capability to determine whether a fossil carbonates can be attributed to biogenic processes, with implications for the record of life on Earth and other terrestrial planets.


Assuntos
Carbonato de Cálcio , Cristalização , Fósseis , Carbonato de Cálcio/química , Carbonato de Cálcio/metabolismo , Animais , Fosfatos de Cálcio/química , Fosfatos de Cálcio/metabolismo , Nephropidae/metabolismo , Nephropidae/química , Biomineralização
6.
J Colloid Interface Sci ; 671: 325-335, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38815369

RESUMO

This present work demonstrated the functional transformation of 3D printed metal substrates into a new family of Surface-enhanced Raman Scattering substrates, a promising approach in developing SERS-based Point-of-care (PoC) analytical platforms. l-Powder Bed Fusion (l-PBF, Additive manufacturing or 3D printing technique) printed metal substrates have rough surfaces, and exhibit high thermal stability and intrinsic chemical inertness, necessitating a suitable surface functionalization approach. This present work demonstrated a unique multi-stage approach to transform l-PBF printed metal structures as recyclable SERS substrates by colloidal carbon templating, chemical vapor deposition, and electroless plating methods sequentially. The surface of the printed metal structures was functionalized using the colloidal carbon soot particles, that were formed by the eucalyptus oil flame deposition method. These carbon particles were shown to interact with the metals present in the printed structures by forming metal carbides and function as an adlayer on the surface. Subsequent deposition of TiO2 onto these templates led to strong grafting of TiO2 and retaining the fractal structure of the soot template onto the metal surface. Electroless deposition of silver nanoparticles resulted in the formation of fractally structured TiO2/Ag nanostructures and these functionalized printed metal structures were shown as excellent SERS substrates in enhancing the vibrational spectral features of Rhodamine B (RhB). The presence of TiO2 photocatalyst on the surface was shown to remove the RhB analyte from the surface under photochemical conditions, which enables the regeneration of SERS activity, and the substrate can be recycled. The migration of metals from the printed metal structures into the fractally ordered TiO2/Ag nanostructures was found to enhance the photocatalytic activity and increase the recyclability of these substrates. This study demonstrates the potential of 3D-printed Inconel metal substrates as next-generation recyclable SERS platforms, offering a substantial advancement over traditional colloidal, thin-film, flexible, and hard SERS substrates.

7.
Chem Commun (Camb) ; 59(90): 13406-13420, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37850470

RESUMO

Combining the design flexibility and rapid prototyping capabilities of additive manufacturing with photocatalytic and plasmonic functionalities is promising for the development of next-generation SERS applications such as point of care diagnostics and in situ monitoring of chemical reactions in fuels and chemical processing. Laser powder bed fusion (LPBF) is a well-matured additive manufacturing technique which generates metallic structures through localised melting and joining of metal powders using a laser. LPBF reduces material wastage during manufacturing, is applicable to a wide range of metals and alloys, and allows printing of complex internal structures. This feature article elaborates the use of soot templating, chemical vapour deposition and electroless plating techniques for grafting plasmonic and semiconductor nanoparticles on the surface of LPBF manufactured metallic substrates. The capability to fabricate different types of intricate metallic lattices using additive manufacturing is demonstrated and technical challenges in their adequate functionalization are elaborated. The developed methodology allows tailoring of the substrate structure, composition, morphology, plasmonic and photocatalytic activities and thus unveils a new class of recyclable SERS substrates.

8.
Molecules ; 28(15)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37570783

RESUMO

Antimetabolites, especially 5-fluorouracil, are commonly used clinically to treat breast, colon, and other cancers. However, their side effects and inefficiency in monotherapy have prompted further searches for new combinations. Thus, the anticancer effect of 5-fluorouracil (5-FU) and the sulforaphane analogue, 4-isoselenocyanato-1-butyl 4'-fluorobenzyl sulfoxide (ISC), were tested in in vitro and in vivo models of triple-negative breast cancer (TNBC) as a new option for this treatment-resistant and aggressive type of breast cancer. A synergic interaction between 5-FU and ISC was observed in the TNBC in vitro model MDA-MB-231 cell line, which led to enhanced antiproliferative effects. The results of in vitro studies were confirmed by in vivo tests, which demonstrated stronger tumor growth inhibition and additive interactions between 5-FU and ISC in the murine TNBC model. Moreover, the results of the body mass and blood analysis showed the safety of the tested combination. The mechanistic study revealed that the combined treatment triggered apoptosis and necrosis, as well as inhibited cell migration.


Assuntos
Antineoplásicos , Neoplasias de Mama Triplo Negativas , Camundongos , Animais , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Antimetabólitos/farmacologia , Antimetabólitos/uso terapêutico , Linhagem Celular Tumoral , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Sulfóxidos/farmacologia , Imunossupressores/farmacologia , Apoptose , Proliferação de Células
9.
Phys Chem Chem Phys ; 25(25): 16796-16806, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37338271

RESUMO

A new tetrahydroacridine derivative (CHDA) with acetylcholinesterase inhibitory properties was synthesized. Using a range of physicochemical techniques, it was shown that the compound strongly adsorbs onto the surface of planar macroscopic or nanoparticulate gold, forming a nearly full monolayer. The adsorbed CHDA molecules reveal well-defined electrochemical behavior, being irreversibly oxidized to electroactive species. The CHDA also exhibits strong fluorescence, which is effectively quenched after adsorption onto gold via a static quenching mechanism. Both CHDA and its conjugate reveal considerable inhibitory properties against acetylcholinesterase activity, which is promising from the perspective of therapeutic application in the treatment of Alzheimer's disease. Moreover, both agents appear to be non-toxic as demonstrated using in vitro studies. On the other hand, conjugation of CHDA with nanoradiogold particles (Au-198) offers new potential diagnostic perspectives in medical imaging.


Assuntos
Doença de Alzheimer , Radioisótopos de Ouro , Nanopartículas Metálicas , Humanos , Doença de Alzheimer/tratamento farmacológico , Acetilcolinesterase , Ouro/química , Radioisótopos de Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química
10.
Materials (Basel) ; 16(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37048881

RESUMO

Titanium alloys are extensively used in various industries due to their excellent corrosion resistance and outstanding mechanical properties. However, titanium alloys are difficult to machine due to their low thermal conductivity and high chemical reactivity with tool materials. In recent years, there has been increasing interest in the use of titanium components produced by additive manufacturing (AM) for a range of high-value applications in aerospace, biomedical, and automotive industries. The machining of additively manufactured titanium alloys presents additional machining challenges as the alloys exhibit unique properties compared to their wrought counterparts, including increased anisotropy, strength, and hardness. The associated higher cutting forces, higher temperatures, accelerated tool wear, and decreased machinability lead to an expensive and unsustainable machining process. The challenges in machining additively manufactured titanium alloys are not comprehensively documented in the literature, and this paper aims to address this limitation. A review is presented on the machining characteristics of titanium alloys produced by different AM techniques, focusing on the effects of anisotropy, porosity, and post-processing treatment of additively manufactured Ti-6Al-4V, the most commonly used AM titanium alloy. The mechanisms resulting in different machining performance and quality are analysed, including the influence of a hybrid manufacturing approach combining AM with conventional methods. Based on the review of the latest developments, a future outlook for machining additively manufactured titanium alloys is presented.

11.
Sci Rep ; 13(1): 3822, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36882485

RESUMO

Otoliths are calcium carbonate components of the stato-acoustical organ responsible for hearing and maintenance of the body balance in teleost fish. During their formation, control over, e.g., morphology and carbonate polymorph is influenced by complex insoluble collagen-like protein and soluble non-collagenous protein assemblages; many of these proteins are incorporated into their aragonite crystal structure. However, in the fossil record these proteins are considered lost through diagenetic processes, hampering studies of past biomineralization mechanisms. Here we report the presence of 11 fish-specific proteins (and several isoforms) in Miocene (ca. 14.8-14.6 Ma) phycid hake otoliths. These fossil otoliths were preserved in water-impermeable clays and exhibit microscopic and crystallographic features indistinguishable from modern representatives, consistent with an exceptionally pristine state of preservation. Indeed, these fossil otoliths retain ca. 10% of the proteins sequenced from modern counterparts, including proteins specific to inner ear development, such as otolin-1-like proteins involved in the arrangement of the otoliths into the sensory epithelium and otogelin/otogelin-like proteins that are located in the acellular membranes of the inner ear in modern fish. The specificity of these proteins excludes the possibility of external contamination. Identification of a fraction of identical proteins in modern and fossil phycid hake otoliths implies a highly conserved inner ear biomineralization process through time.


Assuntos
Fósseis , Membrana dos Otólitos , Animais , Peixes , Proteínas de Peixes , Acústica , Carbonato de Cálcio
12.
Acta Biomater ; 162: 149-163, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37001839

RESUMO

Different non-classical crystallization mechanisms have been invoked to explain structural and compositional properties of biocrystals. The identification of precursor amorphous nanoparticle aggregation as an onset process in the formation of numerous biominerals (crystallization via particle attachment) constituted a most important breakthrough for understanding biologically mediated mineralization. A comprehensive understanding about how the attached amorphous particles transform into more stable, crystalline grains has yet to be elucidated. Here, we document structural, biogeochemical, and crystallographic aspects of the formation as well as the further phase transformations of the amorphous calcium carbonate particles formed by cultured specimens of earthworm Lumbricus terrestris. In-situ observations evidence the formation of proto-vaterite after dehydration of earthworm-produced ACC, which is subsequently followed by proto-vaterite transformation into calcite through nanoparticle attachment within the organic framework. In culture medium spiked with trace amounts of Mn2+, the cauliflower-like proto-vaterite structures become longer-lived than in the absence of Mn2+. We propose that the formation of calcite crystals takes place through a non-classical recrystallization path that involves migration of proto-vaterite nanoparticles to the crystallization site, and then, their transformation into calcite via a dissolution-recrystallization reaction. The latter is complemented by ion-by-ion crystal growth and associated with impurity release. These observations are integrated into a new model of the biocrystallization of earthworm-produced carbonate granules which highlights the sensibility of this process to environmental chemical changes, its potential impact on the bioavailability of contaminants as well as the threat that chemical pollution poses to the normal development of its early stages. STATEMENT OF SIGNIFICANCE: Understanding the mechanisms of nucleation, stabilization and aggregation of amorphous calcium carbonate (ACC) and factors controlling its further transformation into crystalline phases is fundamental for elucidation of biogenic mineralization. Some species of earthworms are natural workbench to understand the biogenic ACC, stabilization and the transformation mechanisms, because they create millimeter-sized calcareous granules from amorphous calcium carbonate, which crystallize to a more stable mineral phase (mostly calcite). This study undergoes into the mechanisms of ACC stabilization by the incorporation of trace elements, as manganese, and the ulterior precipitation of calcareous granules by a coupled process of amorphous particle attachment and ion-by-ion growth. The study points to sensibility of this process to environmental chemical changes.


Assuntos
Carbonato de Cálcio , Oligoquetos , Animais , Carbonato de Cálcio/química , Minerais , Carbonatos , Cristalização
13.
Biomed Pharmacother ; 161: 114490, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36931031

RESUMO

Female breast cancer is the most deadly cancer in women worldwide. The triple-negative breast cancer subtype therapies, due to the lack of specific drug targets, are still based on systemic chemotherapy with doxorubicin, which is burdened with severe adverse effects. To enhance therapeutic success and protect against systemic toxicity, drug carriers or combination therapy are being developed. Thus, an innovative liposomal formulation containing doxorubicin and the main nutraceutical, sulforaphane, has been developed. The anticancer efficacy and safety of the proposed liposomal formulation was evaluated in vivo, in a 4T1 mouse model of triple-negative breast cancer, and the mechanism of action was determined in vitro, using triple-negative breast cancer MDA-MB-231 and non-tumorigenic breast MCF-10A cell line. The elaborated drug carriers were shown to efficiently deliver both compounds into the cancer cell and direct doxorubicin to the cell nucleus. Incorporation of sulforaphane resulted in a twofold inhibition of tumor growth and the potential of up to a fourfold reduction in doxorubicin concentration due to the synergistic interaction between the two compounds. Sulforaphane was shown to increase the accumulation of doxorubicin in the nuclei of cancer cells, accompanied by inhibition of mitosis, without affecting the reactive oxygen species status of the cell. In normal cells, an antagonistic effect resulting in less cytotoxicity was observed. In vivo results showed that sulforaphane incorporation yielded not only cardioprotective, but also nephro- and hepatoprotective effects. The results of the research revealed the prospects of applying sulforaphane as a component of liposomal doxorubicin in triple-negative breast cancer chemotherapy.


Assuntos
Neoplasias de Mama Triplo Negativas , Camundongos , Humanos , Animais , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Doxorrubicina , Lipossomos , Portadores de Fármacos/uso terapêutico , Modelos Animais
14.
Langmuir ; 38(48): 14596-14606, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36395585

RESUMO

Biodegradable polymer particles are of considerable importance due to their multiple applications in medical diagnostics and therapy. Spherical-cap particles have been prepared in a very general and simple method by melting a thin polymer film supported on a solid substrate that is in contact with a hydrophilic solvent. The melted polymer forms droplets which transform into solid particles attached to the surface after cooling down the sample. This approach has been demonstrated for polylactide adlayers on glass, which, when melted in glycerol, produce an array of polymer particles supported on the surface. The size of the particles depends on the experimental conditions and ranges from tens of nanometers to several micrometers. The particles can be employed to incorporate guest species, for example, drug molecules or inorganic nanoparticles. This has been confirmed herein through entrapment of an anticancer drug (doxorubicin) and radiogold (Au-198) nanoparticles. The resulting structures have been examined using a number of complementary physicochemical techniques including scanning and transmission electron microscopy, atomic force and optical microscopy as well as Raman and fluorescence spectroscopy.


Assuntos
Radioisótopos de Ouro , Nanopartículas , Tamanho da Partícula , Nanopartículas/química , Polímeros/química
15.
Materials (Basel) ; 15(15)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35955150

RESUMO

Laparoscopic surgery is undergoing rapid development. Replacing the traditional method of joining cut tissues with sutures or staples could greatly simplify and speed up laparoscopic procedures. This alternative could undoubtedly be adhesives. For decades, scientists have been working on a material to bond tissues together to create the best possible conditions for tissue regeneration. The results of research on tissue adhesives achieved over the past years show comparable treatment effects to traditional methods. Tissue adhesives are a good alternative to surgical sutures in wound closure. This article is a review of the most important groups of tissue adhesives including their properties and possible applications. Recent reports on the development of biological adhesives are also discussed.

16.
Polymers (Basel) ; 14(12)2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35745967

RESUMO

The effective ionic capacities of strong cation ion-exchange resins were investigated and compared using conditions similar to those found in white goods, in order to establish behavioral differences between commercial products and evaluate their capacity in a broader business context. Nine different products of equivalent TDS (Technical Data Sheet) capacity were observed to examine their differences in approximately real-life conditions. For a broader context of applicability analysis, besides the absolute ionic operating capacity, the following additional factors were included in the evaluation: the standard deviation in the resins' performances and their relative prices. A complete method for material applicability evaluation was hereby proposed and shown to offer cost factor benefits of up to 21.1% within the range of products examined, in comparison to a cost-only evaluation for equivalent materials.

17.
Chem Commun (Camb) ; 57(75): 9586-9589, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546248

RESUMO

Selective laser melting printed metal lattice structures functionalised using zeolites have been shown as a promising new generation of catalysts. The unprecedented catalytic activity can be explained by metal migration (most likely chromium) from the support into the zeolite phase making it a promising candidate for endothermic fuels for high-speed flight vehicles.

18.
Sci Rep ; 11(1): 15741, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344911

RESUMO

Gold nanoparticles (AuNPs) decorated with biologically relevant molecules have variety of applications in optical sensing of bioanalytes. Coating AuNPs with small nucleotides produces particles with high stability in water, but functionality-compatible strategies are needed to uncover the full potential of this type of conjugates. Here, we demonstrate that lipoic acid-modified dinucleotides can be used to modify AuNPs surfaces in a controllable manner to produce conjugates that are stable in aqueous buffers and biological mixtures and capable of interacting with nucleotide-binding proteins. Using this strategy we obtained AuNPs decorated with 7-methylguanosine mRNA 5' cap analogs and showed that they bind cap-specific protein, eIF4E. AuNPs decorated with non-functional dinucleotides also interacted with eIF4E, albeit with lower affinity, suggesting that eIF4E binding to cap-decorated AuNPs is partially mediated by unspecific ionic interactions. This issue was overcome by applying lipoic-acid-Tris conjugate as a charge-neutral diluting molecule. Tris-Lipo-diluted cap-AuNPs conjugates interacted with eIF4E in fully specific manner, enabling design of functional tools. To demonstrate the potential of these conjugates in protein sensing, we designed a two-component eIF4E sensing system consisting of cap-AuNP and 4E-BP1-AuNP conjugates, wherein 4E-BP1 is a short peptide derived from 4E-BP protein that specifically binds eIF4E at a site different to that of the 5' cap. This system facilitated controlled aggregation, in which eIF4E plays the role of the agent that crosslinks two types of AuNP, thereby inducing a naked-eye visible absorbance redshift. The reported AuNPs-nucleotide conjugation method based on lipoic acid affinity for gold, can be harnessed to obtain other types of nucleotide-functionalized AuNPs, thereby paving the way to studying other nucleotide-binding proteins.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/metabolismo , Ouro/química , Nanopartículas Metálicas/química , Nucleotídeos/metabolismo , Fragmentos de Peptídeos/química , Capuzes de RNA/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Técnicas Biossensoriais/métodos , Proteínas de Transporte/genética , Proteínas de Ciclo Celular/genética , Humanos , Nucleotídeos/química , Ligação Proteica , Biossíntese de Proteínas , Capuzes de RNA/genética
19.
Materials (Basel) ; 14(8)2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33920743

RESUMO

Implants made of ceramic and metallic elements, which are used in dentistry, may either promote or hinder the colonization and adhesion of bacteria to the surface of the biomaterial to varying degrees. The increased interest in the use of dental implants, especially in patients with chronic systemic diseases such as cystic fibrosis (CF), is caused by an increase in disease complications. In this study, we evaluated the differences in the in vitro biofilm formation on the surface of biomaterials commonly used in dentistry (Ti-6Al-4V, cobalt-chromium alloy (CoCr), and zirconia) by Staphylococcus aureus isolated from patients with CF. We demonstrated that S. aureus adherence and growth depends on the type of material used and its surface topography. Weaker bacterial biofilm formation was observed on zirconia surfaces compared to titanium and cobalt-chromium alloy surfaces. Moreover, scanning electron microscopy showed clear differences in bacterial aggregation, depending on the type of biomaterial used. Over the past several decades, S. aureus strains have developed several mechanisms of resistance, especially in patients on chronic antibiotic treatment such as CF. Therefore, the selection of an appropriate implant biomaterial with limited microorganism adhesion characteristics can affect the occurrence and progression of oral cavity infections, particularly in patients with chronic systemic diseases.

20.
Proc Natl Acad Sci U S A ; 118(3)2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33323482

RESUMO

One of the most conserved traits in the evolution of biomineralizing organisms is the taxon-specific selection of skeletal minerals. All modern scleractinian corals are thought to produce skeletons exclusively of the calcium-carbonate polymorph aragonite. Despite strong fluctuations in ocean chemistry (notably the Mg/Ca ratio), this feature is believed to be conserved throughout the coral fossil record, spanning more than 240 million years. Only one example, the Cretaceous scleractinian coral Coelosmilia (ca. 70 to 65 Ma), is thought to have produced a calcitic skeleton. Here, we report that the modern asymbiotic scleractinian coral Paraconotrochus antarcticus living in the Southern Ocean forms a two-component carbonate skeleton, with an inner structure made of high-Mg calcite and an outer structure composed of aragonite. P. antarcticus and Cretaceous Coelosmilia skeletons share a unique microstructure indicating a close phylogenetic relationship, consistent with the early divergence of P. antarcticus within the Vacatina (i.e., Robusta) clade, estimated to have occurred in the Mesozoic (ca. 116 Mya). Scleractinian corals thus join the group of marine organisms capable of forming bimineralic structures, which requires a highly controlled biomineralization mechanism; this capability dates back at least 100 My. Due to its relatively prolonged isolation, the Southern Ocean stands out as a repository for extant marine organisms with ancient traits.


Assuntos
Exoesqueleto/metabolismo , Antozoários/metabolismo , Calcificação Fisiológica/genética , Carbonato de Cálcio/metabolismo , Exoesqueleto/anatomia & histologia , Exoesqueleto/química , Animais , Antozoários/anatomia & histologia , Antozoários/classificação , Antozoários/genética , Evolução Biológica , Carbonato de Cálcio/química , Fósseis , Filogenia
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