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1.
Int J Mol Sci ; 24(12)2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37373341

RESUMEN

Several studies have highlighted the ability of snail mucus in maintaining healthy skin conditions due to its emollient, regenerative, and protective properties. In particular, mucus derived from Helix aspersa muller has already been reported to have beneficial properties such as antimicrobial activity and wound repair capacity. In order to enhance the beneficial effects of snail mucus, a formulation enriched with antioxidant compounds derived from edible flower waste (Acmella oleracea L., Centaurea cyanus L., Tagetes erecta L., Calendula officinalis L., and Moringa oleifera Lam.) was obtained. UVB damage was used as a model to investigate in vitro the cytoprotective effects of snail mucus and edible flower extract. Results demonstrated that polyphenols from the flower waste extract boosted the antioxidant activity of snail mucus, providing cytoprotective effects in keratinocytes exposed to UVB radiation. Additionally, glutathione content, reactive oxygen species (ROS), and lipid peroxidation levels were reduced following the combined treatment with snail mucus and edible flower waste extract. We demonstrated that flower waste can be considered a valid candidate for cosmeceutical applications due to its potent antioxidant activity. Thus, a new formulation of snail mucus enriched in extracts of edible flower waste could be useful to design innovative and sustainable broadband natural UV-screen cosmeceutical products.


Asunto(s)
Antioxidantes , Cosmecéuticos , Antioxidantes/farmacología , Antioxidantes/análisis , Cosmecéuticos/farmacología , Extractos Vegetales/química , Queratinocitos , Flores/química , Moco/química , Rayos Ultravioleta/efectos adversos
2.
Molecules ; 28(9)2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37175318

RESUMEN

Over the last few years, the study of the SARS-CoV-2 spike protein and its mutations has become essential in understanding how it interacts with human host receptors. Since the crystallized structure of the spike protein bound to the angiotensin-converting enzyme 2 (ACE2) receptor was released (PDB code 6M0J), in silico studies have been performed to understand the interactions between these two proteins. Specifically, in this study, heterocyclic compounds with different chemical characteristics were examined to highlight the possibility of interaction with the spike protein and the disruption of the interaction between ACE2 and the spike protein. Our results showed that these compounds interacted with the spike protein and interposed in the interaction zone with ACE2. Although further studies are needed, this work points to these heterocyclic push-pull compounds as possible agents capable of interacting with the spike protein, with the potential for the inhibition of spike protein-ACE2 binding.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Enzima Convertidora de Angiotensina 2/metabolismo , Unión Proteica
3.
Biotechnol Bioeng ; 118(4): 1456-1465, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33289093

RESUMEN

The heavy metals pollution represents one of the important issues in the environmental field since it is involved in many pathologies from cancer, neurodegenerative, and metabolic diseases. We propose an innovative portable biosensor for the determination of traces of trivalent arsenic (As(III)) and bivalent mercury (Hg(II)) in water. The system implements a strategy combining two advanced sensing modules consisting in (a) a whole cell based on engineered Escherichia coli as selective sensing element towards the metals and (b) an electrochemical miniaturised silicon device with three microelectrodes and a portable reading system. The sensing mechanism relies on the selective recognition from the bacterium of given metals producing the 4-aminophenol redox active mediator detected through a cyclic voltammetry analysis. The miniaturized biosensor is able to operate a portable, robust, and high-sensitivity detection of As(III) with a sensitivity of 0.122 µA ppb-1 , LoD of 1.5 ppb, and a LoQ of 5 ppb. The LoD value is one order of magnitude below of the value indicated to WHO to be dangerous (10 µg/L). The system was proved to be fully versatile being effective in the detection of Hg(II) as well. A first study on Hg(II) showed sensitivity value of 2.11 µA/ppb a LOD value of 0.1 ppb and LoQ value of 0.34 ppb. Also in this case, the detected LOD was 10 times lower than that indicated by WHO (1 ppb). These results pave the way for advanced sensing strategies suitable for the environmental monitoring and the public safety.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Escherichia coli , Mercurio/análisis , Contaminantes Químicos del Agua/análisis , Agua/análisis , Cationes Bivalentes/análisis , Escherichia coli/genética , Escherichia coli/metabolismo
4.
Molecules ; 26(4)2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33669712

RESUMEN

Hydroxyapatite (HA) is the main inorganic mineral that constitutes bone matrix and represents the most used biomaterial for bone regeneration. Over the years, it has been demonstrated that HA exhibits good biocompatibility, osteoconductivity, and osteoinductivity both in vitro and in vivo, and can be prepared by synthetic and natural sources via easy fabrication strategies. However, its low antibacterial property and its fragile nature restricts its usage for bone graft applications. In this study we functionalized a MgHA scaffold with gold nanorods (AuNRs) and evaluated its antibacterial effect against S. aureus and E. coli in both suspension and adhesion and its cytotoxicity over time (1 to 24 days). Results show that the AuNRs nano-functionalization improves the antibacterial activity with 100% bacterial reduction after 24 h. The toxicity study, however, indicates a 4.38-fold cell number decrease at 24 days. Although further optimization on nano-functionalization process are needed for cytotoxicity, these data indicated that Au-NRs nano-functionalization is a very promising method for improving the antibacterial properties of HA.


Asunto(s)
Antiinfecciosos/farmacología , Durapatita/farmacología , Oro/farmacología , Magnesio/farmacología , Nanotubos/química , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Nanotubos/ultraestructura , Espectroscopía de Fotoelectrones , Staphylococcus aureus/efectos de los fármacos , Andamios del Tejido/química
5.
Biotechnol Bioeng ; 117(5): 1554-1561, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31997343

RESUMEN

The development of portable systems for analysis of nucleic acids (NAs) is crucial for the evolution of biosensing in the context of future healthcare technologies. The integration of NA extraction, purification, and detection modules, properly actuated by microfluidics technologies, is a key point for the development of portable diagnostic systems. In this paper, we describe an integrated biosensor platform based on a silicon-plastic hybrid lab-on-disk technology capable of managing NA extraction, purification, and detection processes in an integrated format. The sample preparation process is performed by solid-phase extraction technology using magnetic beads on a plastic disk, while detection is done through quantitative real-time polymerase chain reaction (qRT-PCR) on a miniaturized silicon device. The movement of sample and reagents is actuated by a centrifugal force induced by a disk actuator instrument. The assessment of the NA extraction and detection performance has been carried out by using hepatitis B virus (HBV) DNA genome as a biological target. The quantification of the qRT-PCR chip in the hybrid disk showed an improvement in sensitivity with respect to the qRT-PCR commercial platforms, which means an optimization of time and cost. Limit of detection and limit of quantification values of about 8 cps/reaction and 26 cps/reaction, respectively, were found by using analytical samples (synthetic clone), while the results with real samples (serum with spiked HBV genome) indicate that the system performs as well as the standard methods.


Asunto(s)
Técnicas Biosensibles , Dispositivos Laboratorio en un Chip , Ácidos Nucleicos , ADN Viral/sangre , Hepatitis B/diagnóstico , Virus de la Hepatitis B/genética , Humanos , Límite de Detección , Técnicas Analíticas Microfluídicas , Técnicas de Diagnóstico Molecular , Ácidos Nucleicos/análisis , Ácidos Nucleicos/genética , Ácidos Nucleicos/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa , Extracción en Fase Sólida
6.
Chemistry ; 25(64): 14638-14643, 2019 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-31512779

RESUMEN

A simple and green synthetic protocol for the rapid and effective preparation of Ag, Au and Au@Ag core-shell nanoparticles (NPs) is reported based on the light irradiation of a biocompatible, water-soluble dextran functionalized with benzophenone (BP) in the presence of AgNO3 , HAuCl4 , or both. Photoactivation of the BP moiety produces the highly reducing ketyl radicals through fast (<50 ns) intramolecular H-abstraction from the dextran scaffold, which, in turn, ensures excellent dispersibility of the obtained metal NPs in water. The antibacterial activity of the AgNPs and the photothermal action of the Au@Ag core-shell are also shown.

7.
Biotechnol Bioeng ; 116(8): 2087-2094, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30963547

RESUMEN

In this paper, a miniaturized biosensor containing 96 silicon microchambers electroloaded with nano-volumes of liquid (EW-chip) is presented. The liquid electroloading is achieved by the appropriate modulation of interface properties. The surface chemistries have been studied to guarantee effective interface properties for both electrowetting on dielectric actuation and biocompatibility versus biochemical reactions. The silicon microchambers are 200 nl in volume and are connected to a specific system of electrodes able to deliver liquid sample on each well. The device also integrates temperature sensors and heaters to perform biochemical reactions. On that, the effectiveness of this device has been successfully proven towards the nucleic acids detection via real-time polymerase chain reaction amplification. Hepatitis B virus genome target has been used to assess the device performance. Results show very uniform amplification over the 96 microchambers without any cross-contamination process. These features make this system a very appealing potential solution for genetic point-of-care devices where a high level of parallelism of analysis is required.


Asunto(s)
Técnicas Biosensibles/instrumentación , Dispositivos Laboratorio en un Chip , Ácidos Nucleicos/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa/instrumentación , Silicio/química , Electrodos , Galvanoplastia , Diseño de Equipo
8.
Analyst ; 144(7): 2353-2358, 2019 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-30789186

RESUMEN

An innovative miniaturized silicon-chip was developed for highly sensitive detection of pathogen genomes of both viruses and bacteria through real time PCR (qRT-PCR). The device was properly designed to enhance the optical signal and perform accurate thermal control. Results show an improvement of PCR amplification by one order of magnitude in sensitivity compared to the standard RT-PCR method. In particular for hepatitis B virus a decrease of the mean value of Ct of about 2.9 ± 0.9 compared to the standard system was observed. Similarly, for the bacteria Pseudomonas aeruginosa, Staphylococcus aureus and Acinetobacter baumannii, a decrease of the mean values of Ct of 1.8 ± 0.5, 3.1 ± 0.5 and 3.9 ± 0.9, respectively, was observed.


Asunto(s)
Bacterias/genética , Bacterias/aislamiento & purificación , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa/instrumentación , Silicio , Diseño de Equipo , Genoma Viral/genética , Límite de Detección
9.
Sensors (Basel) ; 18(9)2018 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-30227672

RESUMEN

Surface substrate and chemical functionalization are crucial aspects for the fabrication of the sensitive biosensor based on microarray technology. In this paper, an advanced, silicon-based substrate (A-MA) allowing enhancement of optical signal for microarray application is described. The substrate consists in a multilayer of Si/Al/SiO2 layers. The optical signal enhancement is reached by a combination of the mirror effect of Al film and the SiO2 thickness around 830 nm, which is able to reach the maximum of interference for the emission wavelength of the Cy5 fluorescent label. Moreover, SiO2 layer is suitable for the immobilization of single-strand DNA through standard silane chemistry, and probe densities of about 2000 F/um² are reached. The microarray is investigated in the detection of HBV (Hepatitis B Virus) pathogen with analytical samples, resulting in a dynamic linear range of 0.05⁻0.5 nM, a sensitivity of about 18000 a.u. nM-1, and a Limit of Detection in the range of 0.031⁻0.043 Nm as a function of the capture probe sequence.


Asunto(s)
Técnicas Biosensibles/métodos , Ácidos Nucleicos/análisis , Dióxido de Silicio/química , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación
10.
Sensors (Basel) ; 18(3)2018 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-29495639

RESUMEN

The monitoring of water-soluble pollutants is receiving a growing interest from the scientific community. In this context, sulfide anion species S2- and HS- are particularly relevant since they can cause acute and chronic toxicity including neurological effects and at high concentrations, even death. In this study, a new strategy for fast and sensitive optical detection of sulfide species in water samples is described. The method uses an integrated silicon photomultiplier (SiPM) device coupled with the appropriate analytical strategy applied in a plastic microchip with dried reagents on board. More specifically, all sulfide species (H2S, HS- and S2-) in water samples are detected by the fluorescence signal emitted upon the reaction with N,N-dimethyl-phenylenediamine sulfate in the presence of Fe3+, leading to the formation of the fluorescent methylene blue (MB) species. It has been proven that the system herein proposed is able to measure sulfide concentration in a linear range from 0-10 mg L-1 with a sensitivity value of about 6.7 µA mg-1 L and a detection limit of 0.5 mg L-1. A comparison with conventional UV-Vis detection method has been also carried out. Data show a very good linear correlation (R² = 0.98093), proving the effectiveness of the method. Results pave the way toward the development of portable and low-cost device systems for water-soluble sulfide pollutants.

11.
Sensors (Basel) ; 17(4)2017 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-28398227

RESUMEN

Colorectal cancer (CRC) is an aggressive human malignancy with a complex genomic landscape harboring KRAS mutations. In 40%-60% of patients with CRC, constantly active KRAS proteins affect the prognosis, surgical strategy, and clinical benefit from therapy with anti-epidermal growth factor receptor (EGFR) agents. For this reason, there is a greater demand for minimally-invasive diagnostic devices to characterize the genetic pattern and prevent the acquired mechanism to drug resistance. The rapid developments in cutting-edge diagnostic techniques are expected to play a growing role in medicine and represent an attractive promise to identify potential responders to personalized medicine. Here we propose a new method to simultaneously detect the main KRAS mutations on the portable real-time PCR Q3 platform. This platform is based on hybrid silicon-plastic technology implemented in a miniaturized chip able to achieve a sample-in answer-out rapid analysis, allowing a new approach to genetic counseling and testing.


Asunto(s)
Reacción en Cadena en Tiempo Real de la Polimerasa , Antineoplásicos , Neoplasias Colorrectales , Receptores ErbB , Genotipo , Humanos , Mutación , Proteínas Proto-Oncogénicas p21(ras)
12.
Analyst ; 142(1): 140-146, 2016 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-27917431

RESUMEN

New miniaturised microfluidic biofilter (BF) devices based on silicon micropillars have been developed and tested regarding their ability to extract HBV (Hepatitis B Virus) bacterial DNA from biological sample solutions. The device is composed of a silicon microchannel in which the pillars are distributed at the bottom surface. The extracted DNA solutions were analysed by real time PCR amplification and the biofilter performance was evaluated. The results obtained show that the DNA binding to the biofilters and the elution efficiency strictly depend on the pillars' geometrical dimensions and increase proportionally with the surface/volume ratio. The device exhibiting the best extraction efficiency was then tested in combination with a silicon integrated real time PCR amplification chip as a preliminary step towards the development of genetic point-of-care devices.


Asunto(s)
ADN Bacteriano/aislamiento & purificación , ADN Viral/aislamiento & purificación , Filtración/instrumentación , Dispositivos Laboratorio en un Chip , Silicio , ADN Bacteriano/genética , ADN Viral/genética , Virus de la Hepatitis B/genética , Reacción en Cadena de la Polimerasa , Factores de Tiempo
13.
Genomics ; 103(2-3): 177-82, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24560816

RESUMEN

In the last decades, molecular biology has moved from gene-by-gene analysis to more complex studies using a genome-wide scale. Thanks to high-throughput genomic technologies, such as microarrays and next-generation sequencing, a huge amount of information has been generated, expanding our knowledge on the genetic basis of various diseases. Although some of this information could be transferred to clinical diagnostics, the technologies available are not suitable for this purpose. In this review, we will discuss the drawbacks associated with the use of traditional DNA microarrays in diagnostics, pointing out emerging platforms that could overcome these obstacles and offer a more reproducible, qualitative and quantitative multigenic analysis. New miniaturized and automated devices, called Lab-on-Chip, begin to integrate PCR and microarray on the same platform, offering integrated sample-to-result systems. The introduction of this kind of innovative devices may facilitate the transition of genome-based tests into clinical routine.


Asunto(s)
Genómica/instrumentación , Genómica/métodos , Dispositivos Laboratorio en un Chip , Animales , Genómica/tendencias , Secuenciación de Nucleótidos de Alto Rendimiento/instrumentación , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/tendencias , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos/instrumentación , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos/tendencias , Reacción en Cadena de la Polimerasa/instrumentación , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa/tendencias
14.
Dalton Trans ; 53(16): 7239, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38619044

RESUMEN

Correction for 'Predicting the dye-sensitized solar cell performance of novel linear carbon chain-based dyes: insights from DFT simulations' by Giuseppe Consiglio et al., Dalton Trans., 2023, 52, 15995-16004, https://doi.org/10.1039/D3DT01856C.

15.
RSC Adv ; 14(17): 11676, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38605899

RESUMEN

[This corrects the article DOI: 10.1039/D2RA06767F.].

16.
J Mater Chem B ; 12(4): 952-961, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-37975827

RESUMEN

The development of multifunctional nanohybrid systems for combined photo-induced hyperthermia and drug release is a challenging topic in the research of advanced materials for application in the biomedical field. Here, we report the first example of a three-component red-light-responsive nanosystem consisting of graphene oxide, gold nanoparticles and poly-N-isopropylacrylamide (GO-Au-PNM). The GO-Au-PNM nanostructures were characterized by spectroscopic techniques and atomic force microscopy. They exhibited photothermal conversion effects at various wavelengths, lower critical solution temperature (LCST) behaviour, and curcumin (Curc) loading capacity. The formation of GO-Au-PNM/Curc adducts and photothermally controlled drug release, triggered by red-light excitation (680 nm), were demonstrated using spectroscopic techniques. Drug-polymer interaction and drug-release mechanism were well supported by modelling simulation calculations. The cellular uptake of GO-Au-PNM/Curc was imaged by confocal laser scanning microscopy. In vitro experiments revealed the excellent biocompatibility of the GO-Au-PNM that did not affect the viability of human cells.


Asunto(s)
Curcumina , Grafito , Hipertermia Inducida , Nanopartículas del Metal , Humanos , Polímeros/química , Oro , Línea Celular Tumoral , Luz Roja , Liberación de Fármacos , Hipertermia Inducida/métodos , Curcumina/química
17.
Carbohydr Polym ; 328: 121698, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38220321

RESUMEN

Iodine is a vital microelement and a powerful antiseptic with a rapid and broad spectrum of action. The development of iodophor compounds to improve the solubility and stability of iodine is still challenging. Here, we report the synthesis of a novel cationic ß-cyclodextrin bearing a choline-like pendant (ß-CD-Chol) designed to complex and deliver iodine to bacterial cells. The characterization of ß-CD-Chol and the investigation of the inclusion complex with iodine were performed by NMR spectroscopy, mass spectrometry, UV-vis spectrophotometry, isothermal titration calorimetry, and dynamic light scattering. The functionalization with the positively charged unit conferred improved water-solubility, mucoadhesivity, and iodine complexation efficiency to the ß-CD scaffold. The water-soluble ß-CD-Chol/iodine complex efficiently formed both in solution and by solid-vapor reaction. The solid complex exhibited a significant stability for months. Iodine release from the inclusion complex was satisfactory and the bactericidal activity was proved against a Staphylococcus epidermidis strain. The absence of cytotoxicity tested on human keratinocytes and the improved mucoadhesivity make ß-CD-Chol a promising drug delivery system and an appealing iodophor candidate for iodine-based antisepsis including mucosa disinfection.


Asunto(s)
Yodo , beta-Ciclodextrinas , Humanos , Colina , beta-Ciclodextrinas/química , Yodo/farmacología , Yodo/química , Solubilidad , Antibacterianos/farmacología , Yodóforos , Agua/química , Rastreo Diferencial de Calorimetría , 2-Hidroxipropil-beta-Ciclodextrina/química
18.
Polymers (Basel) ; 16(4)2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38399838

RESUMEN

Polyimides are a polymer class that has been extensively investigated as a membrane material for gas separation owing to its interesting permselective properties in a wide range of operation temperatures and pressures. In order to improve their properties, the addition of different filler types is currently studied. p-tert-Butylcalix[n]arene macrocycles (PTBCs) with different cavity sizes (PTBC4, PTBC6, PTBC8) were used as fillers in a commercial thermoplastic polyimide, with a concentration in the range 1-9 wt%, to develop nanocomposite membranes for gas separation. The selected macrocycles are attractive organic compounds owing to their porous structure and affinity with organic polymers. The nanocomposite membranes were prepared in the form of films in which the polymeric matrix is a continuous phase incorporating the dispersed additives. The preparation was carried out according to a pre-mixing approach in a mutual solvent, and the solution casting was followed by a controlled solvent evaporation. The films were characterized by investigating their miscibility, morphology, thermal and spectral properties. The gas transport through these films was examined as a function of the temperature and also time. The results evidenced that the incorporation of the chosen nanoporous fillers can be exploited to enhance molecular transport, offering additional pathways and promoting rearrangements of the polymeric chains.

19.
Adv Healthc Mater ; 13(16): e2303692, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38508224

RESUMEN

Zero-dimensional boron nitride quantum dots (BNQDs) are arousing interest for their versatile optical, chemical, and biochemical properties. Introducing carbon contents in BNQDs nanostructures is a great challenge to modulate their physicochemical properties. Among the carbon moieties, phenolic groups have attracted attention for their biochemical properties and phenol-containing nanomaterials are showing great promise for biomedical applications. Herein, the first example of direct synthesis of water dispersible BNQDs exposing phenolic and carboxylic groups is presented. The carbon-BNQDs are prepared in a single-step by solvent-assisted reaction of urea with boronic reagents and are characterized by optical absorption, luminescence, Raman, Fourier transform infrared and NMR spectroscopy, X-ray photoelectron spectroscopy, dynamic light scattering, and atomic force microscopy. The carbon-BNQDs exhibit nanodimension, stability, high photothermal conversion efficiency, pH-responsive luminescence and Z-potential. The potential of the carbon-BNQDs to provide photothermal materials in solid by embedding in agarose substrate is successfully investigated. The carbon-BNQDs exhibit biocompatibility on colorectal adenocarcinoma cells (Caco-2) and protective effects from chemical and oxidative stress on Caco-2, osteosarcoma (MG-63), and microglial (HMC-3) cells. Amplicon mRNA-seq analyses for the expression of 56 genes involve in oxidative-stress and inflammation are performed to evaluate the molecular events responsible for the cell protective effects of the carbon-BNQDs.


Asunto(s)
Compuestos de Boro , Carbono , Puntos Cuánticos , Puntos Cuánticos/química , Humanos , Compuestos de Boro/química , Compuestos de Boro/farmacología , Células CACO-2 , Carbono/química , Luminiscencia , Supervivencia Celular/efectos de los fármacos
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