Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47
Filtrar
1.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124433, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38761470

RESUMO

This study focuses on the adsorption process of L-cysteine (Cys), a sulfur-containing amino acid, onto monolayers of gold nanoparticles (AuNPs) prepared through distinct protocols on mica substrates. Two types of AuNPs were prepared using two different methods: the first employed a physical approach, which combined the Inert Gas Condensation (IGC) technique with the magnetron sputtering method, while the second utilized a chemical method involving the reduction of tetrachloroauric acid with trisodium citrate (TC). The characterization of AuNPs was performed using transmission electron microscopy (TEM) and atomic force microscopy (AFM), of up to 5 ± 1.3 nm for bare AuNPs obtained through vacuum techniques, and up to 12 ± 5 nm for negatively charged, citrate-stabilized TCAuNPs(-). The application of spectroscopic techniques based on the surface-enhanced effects allows for describing the adsorption process in both micro- and nanoscale systems: Cys/bare AuNPs and Cys/ TCAuNPs(-). The commonly used surface-enhanced Raman spectroscopy (SERS) technique provided insights into adsorption behaviours at the microscale level. In the case of TCAuNPs(-), an interaction involving the lone electron pair of sulfur (S) atom and metal surface, while on the bare AuNPs, S is adsorbed on the surface, but the cleavage of the SH group is not discernible. Nanoscale analysis was complemented using AFM combined with the surface-enhanced infrared absorption spectroscopy (AFM-SEIRA) technique. AFM-SEIRA map indicated the formation of hot spot which were predominantly located between aggregated TCAuNPs(-) and on specific NPs surfaces (area between NPs and gold-coated tip). Results from the SERS and AFM-SEIRA techniques were in good agreement, underscoring the comprehensive understanding achieved through the chosen experimental approach regarding the Cys interactions with layers of AuNPs.

2.
Int J Mol Sci ; 24(22)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38003646

RESUMO

Mixed manganese-zinc ferrite nanoparticles coated with PEG were studied for their potential usefulness in MRI thermometry as temperature-sensitive contrast agents. Particles in the form of an 8.5 nm core coated with a 3.5 nm layer of PEG were fabricated using a newly developed, one-step method. The composition of Mn0.48Zn0.46Fe2.06O4 was found to have a strong thermal dependence of magnetization in the temperature range between 5 and 50 °C. Nanoparticles suspended in an agar gel mimicking animal tissue and showing non-significant impact on cell viability in the biological test were studied with NMR and MRI over the same temperature range. For the concentration of 0.017 mg/mL of Fe, the spin-spin relaxation time T2 increased from 3.1 to 8.3 ms, while longitudinal relaxation time T1 shows a moderate decrease from 149.0 to 125.1 ms. A temperature map of the phantom exposed to the radial temperature gradient obtained by heating it with an 808 nm laser was calculated from T2 weighted spin-echo differential MR images. Analysis of temperature maps yields thermal/spatial resolution of 3.2 °C at the distance of 2.9 mm. The experimental relaxation rate R2 data of water protons were compared with those obtained from calculations using a theoretical model incorporating the motion averaging regime.


Assuntos
Meios de Contraste , Nanopartículas , Animais , Temperatura , Meios de Contraste/química , Imageamento por Ressonância Magnética/métodos , Água , Nanopartículas/química
3.
ACS Biomater Sci Eng ; 9(12): 6658-6669, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37991876

RESUMO

To construct their shells, molluscs are able to produce a large array of calcified materials including granular, prismatic, lamellar, fibrous, foliated, and plywood-like microstructures. The latter includes an aragonitic (the crossed-lamellar) and a calcitic (the crossed-foliated) variety, whose modes of formation are particularly enigmatic. We studied the crossed-foliated calcitic layers secreted solely by members of the limpet family Patellidae using scanning and transmission electron microscopy and electron backscatter diffraction. From the exterior to the interior, the material becomes progressively organized into commarginal first-order lamellae, with second and third order lamellae dipping in opposite directions in alternating lamellae. At the same time, the crystallographic texture becomes stronger because each set of the first order lamellae develops a particular orientation for the c-axis, while both sets maintain common orientations for one {104} face (parallel to the growth surface) and one a-axis (perpendicular to the planes of the first order lamellae). Each first order lamella shows a progressive migration of its crystallographic axes with growth in order to adapt to the orientation of the set of first order lamellae to which it belongs. To explain the progressive organization of the material, we hypothesize that a secretional zebra pattern, mirrored by the first order lamellae on the shell growth surface, is developed on the shell-secreting mantle surface. Cells belonging to alternating stripes behave differently to determine the growth orientation of the laths composing the first order lamellae. In this way, we provide an explanation as to how plywood-like materials can be fabricated, which is based mainly on the activity of mantle cells.


Assuntos
Carbonato de Cálcio , Microscopia Eletrônica de Varredura , Carbonato de Cálcio/química
4.
Heliyon ; 9(10): e20572, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37842606

RESUMO

The presence of pesticides in our environment is a consequence of intensive industrial and civilizational development, necessitating the search for effective and safe methods to remove them. We suggest utilizing zeolite X and a zeolite-carbon composite, obtained through the chemical transformation of fly ash, as pesticide sorbents. To increase the sorption efficiency of 2,4-dichlorophenoxyacetic acid (2,4-D), 2-methyl-4-chlorophenoxyacetic acid (MCPA), carbendazim, and simazine, we functionalized the zeolite materials with cationic (hexadecyltrimethylammonium) and nonionic (Triton X-100) surfactants. We used transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), thermogravimetric/differential thermal analysis (TG/DTA) and point of zero charge (pHpzc) analysis to characterize the functionalized sorbent materials. Our results indicate that cationic surfactants significantly enhance the adsorption of 2,4-D and MCPA. In contrast, carbendazim and simazine exhibit maximum sorption on the unmodified zeolite-carbon composite. The sorption mechanism is intricate, with physical sorption predominating, primarily due to electrostatic interactions between the protonated binding sites of the adsorbents and the negatively charged pesticide molecules. Regeneration tests demonstrated that ethanol is the most effective in regenerating zeolite-carbon composite with adsorbed MCPA and 2,4-D, while thermal regeneration was not possible. Adsorbents with simazine and carbendazim can be regenerated using both thermal and ethanol methods, but the thermal regeneration of zeolite with adsorbed simazine is more efficient. Utilizing functionalized zeolite materials obtained from industrial waste, such as fly ash, could provide an efficient way to remove pesticides from the environment.

6.
RSC Adv ; 13(32): 21971-21981, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37483675

RESUMO

Tissue engineering is a burgeoning field focused on repairing damaged tissues through the combination of bodily cells with highly porous scaffold biomaterials, which serve as templates for tissue regeneration, thus facilitating the growth of new tissue. Carbon materials, constituting an emerging class of superior materials, are currently experiencing remarkable scientific and technological advancements. Consequently, the development of novel 3D carbon-based composite materials has become significant for biomedicine. There is an urgent need for the development of hybrids that will combine the unique bioactivity of ceramics with the performance of carbonaceous materials. Considering these requirements, herein, we propose a straightforward method of producing a 3D carbon-based scaffold that resembles the structural features of spongin, even on the nanometric level of their hierarchical organization. The modification of spongin with calcium phosphate was achieved in a deep eutectic solvent (choline chloride : urea, 1 : 2). The holistic characterization of the scaffolds confirms their remarkable structural features (i.e., porosity, connectivity), along with the biocompatibility of α-tricalcium phosphate (α-TCP), rendering them a promising candidate for stem cell-based tissue-engineering. Culturing human bone marrow mesenchymal stem cells (hMSC) on the surface of the biomimetic scaffold further verifies its growth-facilitating properties, promoting the differentiation of these cells in the osteogenesis direction. ALP activity was significantly higher in osteogenic medium compared to proliferation, indicating the differentiation of hMSC towards osteoblasts. However, no significant difference between C and C-αTCP in the same medium type was observed.

7.
Nanoscale Adv ; 5(11): 3063-3074, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37260483

RESUMO

Well-organized, spherical, mesoporous hollow @CuMgAl-LDHs (layered double hydroxides) are prepared by the controlled removal of the SiO2 from SiO2@CuMgAl-LDH core-shell hybrids that in turn are synthesized via a bottom-up strategy. The materials are prepared with various Cu/Mg molar ratios (Cu/Mg = 0.05-0.50) while keeping the ratio of Cu and Mg constant, (Cu + Mg)/Al = 2. The effect of Cu doping and the silica core removal process (conducted for 4 h at 30 °C using 1 M NaOH) on the chemical composition, morphology, structure, texture and reducibility of the resulting materials are described. @CuMgAl-MOs (mixed oxides) obtained by thermal treatment of the @CuMgAl-LDHs are active and selective catalysts for the selective catalytic reduction of NOx using ammonia, and effectively operate at low temperatures. The N2 yield increases with increased Cu content in the CuMgAl shell, which is associated with the easier reducibility of the Cu species incorporated into the MgAl matrix. @CuMgAl-MOs show better catalytic performance than bulk CuMgAl MOs.

8.
Methods Appl Fluoresc ; 11(3)2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37220759

RESUMO

Polyvinylpyrrolidone (PVP) can be used to produce upconversion nanoparticles (UCNPs) in an advantageous manner, i.e. at modest temperatures in open-to-air conditions with simple hotplate and flask apparatus. However, the influence of PVP parameters on the formation of UCNPs has not been previously investigated. In this exploratory study, we establish that PVP molecular weight and relative amount of PVP can greatly influence the morphology and diameter of NaYF4:Yb,Er UCNPs produced via the PVP-assisted route. At nominal amounts of PVP, varying the molecular weight of PVP in synthesis between 10,000 g mol-1(PVP10), 40,000 g mol-1(PVP40), and 55,000 g mol-1(PVP55), had minimal effect on UCNP morphology, whereas reducing the quantity of PVP10 and PVP40 in the reaction to 10% of the nominal amount resulted in two notable effects: (1) the generation of a greater range of UCNP diameters and (2) the production of an unexpected sub-population of rhombus-shaped UCNPs. Bulk and individual nanoparticle analysis indicates that all UCNP morphologies were cubic (α-phase) crystal structure and consisted of NaYF4:Yb,Er. Optical emission properties exhibited only modest green and red luminescence emission ratio when PVP parameters were varied. However, separately produced PVP40 NaYF4:Yb,Tm UCNPs exhibited a much more intense and dual-band blue/red emission. This exploratory work demonstrates that tailoring PVP content in synthesis of UCNPs can greatly alter morphology of UCNPs produced and should be carefully considered in experimental design. However, the underlying mechanisms of action of the role PVP plays in this synthesis remain unclear. Ultimately, significant further work is still required to fully elucidate the relevant chemistry to achieve full control of PVP-UCNP synthesis.

9.
Int J Mol Sci ; 24(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36982758

RESUMO

The aim of this project is to fabricate hydrogen-rich silicone doped with magnetic nanoparticles for use as a temperature change indicator in magnetic resonance imaging-guided (MRIg) thermal ablations. To avoid clustering, the particles of mixed MnZn ferrite were synthesized directly in a medical-grade silicone polymer solution. The particles were characterized by transmission electron microscopy, powder X-ray diffraction, soft X-ray absorption spectroscopy, vibrating sample magnetometry, temperature-dependent nuclear magnetic resonance relaxometry (20 °C to 60 °C, at 3.0 T), and magnetic resonance imaging (at 3.0 T). Synthesized nanoparticles were the size of 4.4 nm ± 2.1 nm and exhibited superparamagnetic behavior. Bulk silicone material showed a good shape stability within the study's temperature range. Embedded nanoparticles did not influence spin-lattice relaxation, but they shorten the longer component of spin-spin nuclear relaxation times of silicone's protons. However, these protons exhibited an extremely high r2* relaxivity (above 1200 L s-1 mmol-1) due to the presence of particles, with a moderate decrease in the magnetization with temperature. With an increased temperature decrease of r2*, this ferro-silicone can be potentially used as a temperature indicator in high-temperature MRIg ablations (40 °C to 60 °C).


Assuntos
Manganês , Nanopartículas , Prótons , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Zinco/química
10.
ACS Appl Mater Interfaces ; 14(37): 42057-42070, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36094407

RESUMO

Benefits emerging from applying high-entropy ceramics in Li-ion technology are already well-documented in a growing number of papers. However, an intriguing question may be formulated: how can the multicomponent solid solution-type material ensure stable electrochemical performance? Utilizing an example of nonequimolar Sn-based Sn0.8(Co0.2Mg0.2Mn0.2Ni0.2Zn0.2)2.2O4 high-entropy spinel oxide, we provide a comprehensive model explaining the observed very good cyclability. The material exhibits a high specific capacity above 600 mAh g-1 under a specific current of 50 mA g-1 and excellent capacity retention near 100% after 500 cycles under 200 mA g-1. The stability originates from the conversion-alloying reversible reactivity of the amorphous matrix, which forms during the first lithiation from the initial high-entropy structure, and preserves the high level of cation disorder at the atomic scale. In the altered Li-storage mechanism in relation to the simple oxides, the unwanted aggregated metallic grains are not exsolved from the anode and therefore do not form highly lithiated phases characterized by large volumetric changes. Also, the electrochemical activity of Mg from the oxide matrix can be clearly observed. Because the studied compound was prepared by a conventional solid-state route, implementation of the presented approach is facile and appears usable for any oxide anode material containing a high-entropy mixture of elements.

11.
BMC Vet Res ; 18(1): 298, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922808

RESUMO

High stocking densities, closed animal houses, and elevated concentrations of bacteria, fungi, and the products of their activity, including ammonia and hydrogen sulphide, have adverse health effects. Active techniques used to reduce unfavourable environmental conditions, such as ventilation, sprinkling, bedding sorbents, and nutritional treatments, are not always sufficient to improve the animals' living environment. The current paper aims to evaluate the effect of radiant catalytic ionization (RCI) on airborne microorganisms, cage microbiological status, gaseous ammonia concentrations, and the haematological status of mice in animal houses. After one week of operation of an RCI system, the number of airborne bacteria and fungi in the experimental room decreased in comparison to the first day of the experiment (p < 0.05 and p < 0.05 respectively), as did the concentrations of ammonia (p < 0.01) and dust. At the same time, the basic health parameters of the mice, determined in the blood, were very similar between the control and experimental room. RCI seems to be an ideal solution to ensure high hygiene standards in animal rooms and houses with limited use of disinfectants or antibiotic treatment of sick animals. An additional, environmental benefit is the limited amount of nitrogen released.


Assuntos
Amônia , Roedores , Alérgenos , Amônia/análise , Animais , Bactérias , Poeira/análise , Fungos , Abrigo para Animais , Camundongos , Ventilação
12.
Chem Mater ; 34(9): 4001-4018, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35573108

RESUMO

Superparamagnetic ferrite nanoparticles coated with a polymer layer are widely used for biomedical applications. The objective of this work is to design nanoparticles as a magnetic resonance imaging (MRI) temperature-sensitive contrast agent. Copper-zinc ferrite nanoparticles coated with a poly(ethylene glycol) (PEG) layer are synthesized using a one-step thermal decomposition method in a polymer matrix. The resulting nanoparticles are stable in water and biocompatible. Using Mössbauer spectroscopy and magnetometry, it was determined that the grown nanoparticles exhibit superparamagnetic properties. Embedding these particles into an agarose gel resulted in significant modification of water proton relaxation times T 1, T 2, and T 2* determined by nuclear magnetic resonance measurements. The results of the spin-echo T 2-weighted MR images of an aqueous phantom with embedded Cu0.08Zn0.54Fe2.38O4 nanoparticles in the presence of a strong temperature gradient show a strong correlation between the temperature and the image intensity. The presented results support the hypothesis that CuZn ferrite nanoparticles can be used as a contrast agent for MRI thermometry.

13.
Chem Mater ; 34(2): 809-825, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35095188

RESUMO

A new indium precursor, namely, indium(II) chloride, was tested as a precursor in the synthesis of ternary Ag-In-S and quaternary Ag-In-Zn-S nanocrystals. This new precursor, being in fact a dimer of Cl2In-InCl2 chemical structure, is significantly more reactive than InCl3, typically used in the preparation of these types of nanocrystals. This was evidenced by carrying out comparative syntheses under the same reaction conditions using these two indium precursors in combination with the same silver (AgNO3) and zinc (zinc stearate) precursors. In particular, the use of indium(II) chloride in combination with low concentrations of the zinc precursor yielded spherical-shaped (D = 3.7-6.2 nm) Ag-In-Zn-S nanocrystals, whereas for higher concentrations of this precursor, rodlike nanoparticles (L = 9-10 nm) were obtained. In all cases, the resulting nanocrystals were enriched in indium (In/Ag = 1.5-10.3). Enhanced indium precursor conversion and formation of anisotropic, longitudinal nanoparticles were closely related to the presence of thiocarboxylic acid type of ligands in the reaction mixture. These ligands were generated in situ and subsequently bound to surfacial In(III) cations in the growing nanocrystals. The use of the new precursor of enhanced reactivity facilitated precise tuning of the photoluminescence color of the resulting nanocrystals in the spectral range from ca. 730 to 530 nm with photoluminescence quantum yield (PLQY) varying from 20 to 40%. The fabricated Ag-In-S and Ag-In-Zn-S nanocrystals exhibited the longest, reported to date, photoluminescence lifetimes of ∼9.4 and ∼1.4 µs, respectively. It was also demonstrated for the first time that ternary (Ag-In-S) and quaternary (Ag-In-Zn-S) nanocrystals could be applied as efficient photocatalysts, active under visible light (green) illumination, in the reaction of aldehydes reduction to alcohols.

14.
Rejuvenation Res ; 24(6): 441-448, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34918960

RESUMO

Mesenchymal stromal cells from adipose tissue (adipose stromal cells, ASCs) are regulators of repair processes in situ by paracrine mechanisms. These unique capabilities make ASCs candidates for the regenerative medicine applications, including cell-assisted lipotransfer method. ASC aging processes have been extensively researched in vitro, there is however limited information about the impact of ASC aging on their biological role in tissue regeneration in vivo. The aim of our study was the research of the possible effects of aging processes of ASCs resulting from the donor age or from in vitro aging during long-term culture (ASC expansion in bioreactors) on their capability to support survival of adipose subcutaneous transplants in rats. The supportive in vivo effects of ASCs from young donors were compared with the effects of ASCs from old donors and ASCs "aged" in long-term in vitro cultures. Fat grafts enriched with ASCs (regardless of their age) retain their volume longer than fat grafts without ASCs supplementation. Vascular expansion in cell-enriched fat grafts was more intense when compared with the controls. It may be concluded that the aging of ASCs does not substantially reduce their ability for the support of the survival of adipose tissue grafts.


Assuntos
Células-Tronco Mesenquimais , Tecido Adiposo , Animais , Técnicas de Cultura de Células , Ratos , Medicina Regenerativa
15.
Materials (Basel) ; 14(23)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34885470

RESUMO

Yttrium iron garnet was obtained using four methods of synthesis. A modified citrate method and a modified citrate method with YIG (yttrium iron garnet, Y3Fe5O12) nucleation were used. In two subsequent methods, YIP (yttrium iron perovskite, YFeO3) and α-Fe2O3 obtained in the first case by the citrate method and in the second by precipitation of precursors with an ammonia solution were used as the input precursors for reaction sintering. Differential scanning calorimetry (DSC) measurements of the output powders obtained by all methods allowed to identify the effects observed during the temperature increase. Dilatometric measurements allowed to determine the changes in linear dimensions at individual stages of reaction sintering. In the case of materials obtained by the citrate method, two effects occur with the increasing temperature, the first of which corresponds to the reaction of the formation of yttrium iron perovskite (YIP), and the second is responsible for the reaction of the garnet (YIG) formation. However, in the case of heat treatment of the mixture of YIP and α-Fe2O3, we observe only the effect responsible for the solid state reaction leading to the formation of yttrium iron garnet. The obtained materials were reaction sintered at temperatures of 1300 and 1400 °C. Only in the case of material obtained from a mixture of perovskite and iron(III) oxide obtained by ammonia precipitation at temperature of 1400 °C were densities achieved higher than 98% of the theoretical density. The use of Hot Isostatic Pressing (HIP) in the case of this material allowed to eliminate the remaining porosity and to obtain full density.

16.
Sci Rep ; 11(1): 21808, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750434

RESUMO

Although the key factor affecting the biocompatibility of IONPs is the core size, there is a lack of regular investigation concerning the impact of the parameter on the toxicity of these nanomaterials. Therefore, such studies were carried out in this paper. Their purpose was to compare the influence of PEG-coated-magnetite NPs with the core of 5, 10 and 30 nm on six carefully selected cell lines. The proliferation rate, viability, metabolic activity, migration activity, ROS levels and cytoskeleton architecture of cells have been evaluated for specified incubation periods. These were 24 and 72-h long incubations with IONPs administered in two doses: 5 and 25 µg Fe/ml. A decrease in viability was observed after exposure to the tested NPs for all the analyzed cell lines. This effect was not connected with core diameter but depended on the exposure time to the nanomaterials. IONPs increased not only the proliferation rate of macrophages-being phagocytic cells-but also, under certain conditions stimulated tumor cell divisions. Most likely, the increase in proliferation rate of macrophages contributed to the changes in the architecture of their cytoskeleton. The growth in the level of ROS in cells had been induced mainly by the smallest NPs. This effect was observed for HEK293T cells and two cancerous lines: U87MG (at both doses tested) and T98G (only for the higher dose). This requires further study concerning both potential toxicity of such IONPs to the kidneys and assessing their therapeutic potential in the treatment of glioblastoma multiforme.


Assuntos
Linhagem Celular/efeitos dos fármacos , Nanopartículas Magnéticas de Óxido de Ferro/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Linhagem Celular/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Movimento Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Células HEK293/efeitos dos fármacos , Células HEK293/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Nanopartículas Magnéticas de Óxido de Ferro/administração & dosagem , Nanopartículas Magnéticas de Óxido de Ferro/ultraestrutura , Camundongos , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo
17.
Cancer Res ; 81(23): 6029-6043, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34625423

RESUMO

The family of PIM serine/threonine kinases includes three highly conserved oncogenes, PIM1, PIM2, and PIM3, which regulate multiple prosurvival pathways and cooperate with other oncogenes such as MYC. Recent genomic CRISPR-Cas9 screens further highlighted oncogenic functions of PIMs in diffuse large B-cell lymphoma (DLBCL) cells, justifying the development of small-molecule PIM inhibitors and therapeutic targeting of PIM kinases in lymphomas. However, detailed consequences of PIM inhibition in DLBCL remain undefined. Using chemical and genetic PIM blockade, we comprehensively characterized PIM kinase-associated prosurvival functions in DLBCL and the mechanisms of PIM inhibition-induced toxicity. Treatment of DLBCL cells with SEL24/MEN1703, a pan-PIM inhibitor in clinical development, decreased BAD phosphorylation and cap-dependent protein translation, reduced MCL1 expression, and induced apoptosis. PIM kinases were tightly coexpressed with MYC in diagnostic DLBCL biopsies, and PIM inhibition in cell lines and patient-derived primary lymphoma cells decreased MYC levels as well as expression of multiple MYC-dependent genes, including PLK1. Chemical and genetic PIM inhibition upregulated surface CD20 levels in an MYC-dependent fashion. Consistently, MEN1703 and other clinically available pan-PIM inhibitors synergized with the anti-CD20 monoclonal antibody rituximab in vitro, increasing complement-dependent cytotoxicity and antibody-mediated phagocytosis. Combined treatment with PIM inhibitor and rituximab suppressed tumor growth in lymphoma xenografts more efficiently than either drug alone. Taken together, these results show that targeting PIM in DLBCL exhibits pleiotropic effects that combine direct cytotoxicity with potentiated susceptibility to anti-CD20 antibodies, justifying further clinical development of such combinatorial strategies. SIGNIFICANCE: These findings demonstrate that inhibition of PIM induces DLBCL cell death via MYC-dependent and -independent mechanisms and enhances the therapeutic response to anti-CD20 antibodies by increasing CD20 expression.


Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-pim-1/antagonistas & inibidores , Rituximab/farmacologia , Animais , Antígenos CD20 , Antineoplásicos Imunológicos/farmacologia , Apoptose , Proliferação de Células , Feminino , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Camundongos , Camundongos SCID , Fosforilação , Proteínas Proto-Oncogênicas c-myc/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Int J Mol Sci ; 22(18)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34575867

RESUMO

Some misfolded proteins, e.g., immunoglobulin monoclonal free light chains (FLC), tend to form fibrils. Protein deposits in tissue may lead to amyloidosis and dysfunction of different organs. There is currently no technique allowing for the identification of FLC that are prone to aggregate. The development of such a method would enable the early selection of patients at high risk of developing amyloidosis. The aim of this study was to investigate whether silver nanoparticles (AgNPs) could be a useful tool to study the process of aggregation of FLC and their susceptibility to form the protein deposits. Mixtures of AgNPs and urine samples from patients with multiple myeloma were prepared. To evaluate the aggregation process of nanoparticles coated with proteins, UV-visible spectroscopy, transmission electron microscopy, and the original laser light scattering method were used. It has been shown that some clones of FLC spontaneously triggered aggregation of the nanoparticles, while in the presence of others, the nanoparticle solution became hyperstable. This is probably due to the structure of the chains themselves, unique protein-AgNPs interactions and perhaps correlates with the tendency of some FLC clones to form deposits. Nanoparticle technology has proven to be helpful in identifying clones of immunoglobulin FLC that tend to aggregate.


Assuntos
Anticorpos Monoclonais/química , Cadeias Leves de Imunoglobulina/sangue , Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Nanopartículas Metálicas/química , Mieloma Múltiplo/sangue , Mieloma Múltiplo/imunologia , Prata/química , Amiloidose/metabolismo , Humanos , Cadeias Leves de Imunoglobulina/química , Cadeias kappa de Imunoglobulina/química , Cadeias lambda de Imunoglobulina/química , Testes Imunológicos , Lasers , Luz , Microscopia Eletrônica de Transmissão , Nanomedicina , Dobramento de Proteína , Espalhamento de Radiação
19.
Nanoscale ; 13(22): 10152-10166, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34075933

RESUMO

The aim of this work was to investigate how chemical functionalization affects the electronic properties of multi-walled carbon nanotubes, altering the electrophoretic deposition process: a method of choice for the fabrication of high quality, all-carbon nanotube (CNT) layers. Wet chemistry methods were applied to modify the surfaces of CNTs by insertion of various oxygen- and nitrogen-containing groups. Transmission electron microscopy revealed no significant changes in the material morphology, while X-ray photoelectron spectroscopy and Raman spectroscopy showed that changes in the chemical composition did not translate to the changes in the structure. Molecularly modelled optimized surface functional group geometries and electron density distributions allowed the calculation of the dipole moments (-COOH = 0.77; -OH = 1.65; -CON(CH3CH2)2 = 3.33; -CONH2 = 2.00; -NH2 = 0.78). Due to their polarity, the introduction of surface functional groups resulted in significant modifications of the electronic properties of CNTs, as elucidated by work function measurements via the Kelvin method and ultraviolet photoelectron spectroscopy. The work function changed from 4.6 eV (raw CNTs) to 4.94 eV for the -OH functionalized CNTs and 4.3 eV for the CNTs functionalized with -CON(CH3CH2), and was inversely proportional to the dipole moment values. Finally, using CNT dispersions, electrophoretic deposition was conducted, allowing the correlation of the work function of CNTs and the measured electrophoretic current with the impact on the deposits' qualities. Thus, a rational background for the development of carbon-based biomaterials was provided.

20.
Int J Mol Sci ; 22(6)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808900

RESUMO

TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein capable of selectively inducing apoptosis in cancer cells by binding to its cognate receptors. Here, we examined the anticancer efficacy of a recently developed chimeric AD-O51.4 protein, a TRAIL fused to the VEGFA-originating peptide. We tested AD-O51.4 protein activity against human colorectal cancer (CRC) models and investigated the resistance mechanism in the non-responsive CRC models. The quantitative comparison of apoptotic activity between AD-O51.4 and the native TRAIL in nine human colorectal cancer cell lines revealed dose-dependent toxicity in seven of them; the immunofluorescence-captured receptor abundance correlated with the extent of apoptosis. AD-O51.4 reduced the growth of CRC patient-derived xenografts (PDXs) with good efficacy. Cell lines that acquired AD-O51.4 resistance showed a significant decrease in surface TRAIL receptor expression and apoptosis-related proteins, including Caspase-8, HSP60, and p53. These results demonstrate the effectiveness of AD-O51.4 protein in CRC preclinical models and identify the potential mechanism underlying acquired resistance. Progression of AD-O51.4 to clinical trials is expected.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Recombinantes de Fusão/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Camundongos , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/química , Ligante Indutor de Apoptose Relacionado a TNF/genética , Fator A de Crescimento do Endotélio Vascular/química , Fator A de Crescimento do Endotélio Vascular/genética , Ensaios Antitumorais Modelo de Xenoenxerto
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA