Our Publications Database

Article 46

Influence of surfactant-tailored Mn-doped ZnO nanoparticles on ROS production and DNA damage induced in murine fibroblast cells

Traian Popescu, Christien Oktaviani Matei, Ioana Dorina Vlaicu, Ioan Tivig, Andrei Cristian Kuncser, Mariana Stefan, Daniela Ghica, Luminita Claudia Miclea, Tudor Savopol, Daniela Cristina Culita, Mihaela Georgeta Moisescu

Journal: Nature Scientific Reports

Year: 2020

DOI: 10.1038/s41598-020-74816-0

Cell biology, Chemistry, Materials science

     The present study concerns the in vitro oxidative stress responses of non-malignant murine cells exposed to surfactant-tailored ZnO nanoparticles (NPs) with distinct morphologies and different levels of manganese doping. Two series of Mn-doped ZnO NPs were obtained by coprecipitation synthesis method, in the presence of either polyvinylpyrrolidone (PVP) or sodium hexametaphosphate (SHMTP). The samples were investigated by powder X-ray Diffraction, Transmission Electron Microscopy, Fourier-Transform Infrared and Electron Paramagnetic Resonance spectroscopic methods, and N2 adsorption-desorption analysis. The observed surfactant-dependent effects concerned: i) particle size and morphology; ii) Mn-doping level; iii) specific surface area and porosity. The relationship between the surfactant dependent characteristics of the Mn-doped ZnO NPs and their in vitro toxicity was assessed by studying the cell viability, intracellular reactive oxygen species (ROS) generation, and DNA fragmentation in NIH3T3 fibroblast cells. The results indicated a positive correlation between the specific surface area and the magnitude of the induced toxicological effects and suggested that Mn-doping exerted a protective effect on cells by diminishing the pro-oxidative action associated with the increase in the specific BET area. The obtained results support the possibility to modulate the in vitro toxicity of ZnO nanomaterials by surfactant-controlled Mn-doping.

Article 45

Effect of Nanoconfinement of Polyphenolic Extract from Grape Pomace into Functionalized Mesoporous Silica on Its Biocompatibility and Radical Scavenging Activity

Ana-Maria Brezoiu, Laura Bajenaru, Daniela Berger, Raul-Augustin Mitran, Mihaela Deaconu, Daniel Lincu, Anicuta Stoica Guzun, Cristian Matei, Mihaela Georgeta Moisescu , Ticuta Negreanu-Pirjol

Journal: Antioxidants

Year: 2020

DOI: 10.3390/antiox9080696 

Functionalized mesoporous silica; Polyphenolic extract; Polyphenolic extract encapsulation; Polyphenols delivery profile; Radical scavenger activity

The aim of this paper is to assess the properties of Mamaia (MM) grape pomace polyphenolic extract loaded onto pristine and functionalized MCM-41 mesoporous silica as potential ingredients for nutraceuticals or cosmetics. The chemical profile of hydroalcoholic polyphenolic extracts, prepared either by conventional extraction or microwave-assisted method, was analyzed by reverse-phase high-performance liquid chromatography with photodiode array detector (HPLC-PDA) analysis, while their radical scavenger activity (RSA) was evaluated using DPPH (2,2-diphenyl-1-picrylhydrazyl radical) and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) assays. The extract-loaded materials were characterized by Fourier transform infrared (FTIR) spectroscopy, N2 adsorption-desorption isotherms, thermogravimetric analysis, as well as RSA (DPPH and ABTS assays). The polyphenols release profiles from pristine and functionalized (with mercaptopropyl, propyl sulfonic acid, cyanoethyl and propionic acid moieties) MCM-41-type supports were determined in phosphate buffer solution (PBS) pH 5.7. For selected materials containing embedded phytochemicals, cellular viability, and oxidative stress level on immortalized mouse embryonic fibroblast cell line (NIH3T3) were evaluated. A more acidic functional groups linked on silica pore walls determined a higher amount of phytochemicals released in PBS. The extract-loaded materials showed a good cytocompatibility on tested concentrations. The embedded extract preserved better the RSA over time than the free extract. The polyphenols-loaded MCM-41-type silica materials, especially MM@MCM-COOH material, demonstrated a good in vitro antioxidant effect on NIH3T3 cells, being potential candidates for nutraceutical or cosmetic formulations.

Article 44

Effects of Ibrutinib on biophysical parameters of platelet in patients with chronic lymphocytic leukaemia

Popov, Viola Maria; Matei, Christien Oktaviani; Omer, Meilin; Onisai, Minodora; Matei, Mircea Bogdan; Savopol, Tudor; Bumbea,Horia; Moisescu, Mihaela G.

Journal: American Journal of Blood Research

Year: 2020

ISSN:2160-1992

  

 

Ibrutinib; leukemia; platelets; membrane potential; ROS

Patients with chronic lymphocytic leukemia (CLL) treated with Ibrutinib often present hemorrhagic complications. Platelets dysfunction is well documented by aggregometry and flow cytometry, but the mechanisms by which Ibrutinib treatment influences the platelets status is yet to be evaluated. The aim of this study is to identify platelet membrane parameters in chronic lymphocytic leukemia (CLL) that could be altered by Ibrutinib administration. In this paper we propose a set of fluorescence measurements of the following parameters: membrane fluidity, resting membrane potential, and reactive oxygen species production of platelets suspensions obtained from CLL patients treated or not with Ibrutinib as markers for platelets status in this pathological situation. Platelets from CLL patients treated with Ibrutinib have higher membrane fluidity, lower resting membrane potential and higher level of reactive oxygen species production compared to the untreated CLL patients. These patients are also presenting higher membrane fluidity and lower resting membrane potential compared to healthy volunteers.

 

Article 43

Microscopic observation of living cells during their exposure to modulated electromagnetic fields

Sandu, Ana-Maria; Ungureanu, Mihaela A.; Morega, Mihaela; Calin, Violeta L., Moisescu, Mihaela G.; Paun, Irina A.; Mihailescu, Mona

Journal: Advanced topics in optoelectronics, microelectronics and nanotechnologies x

Year: 2020

DOI: 10.1117/12.2571092

Cell electroporation; Finite element modeling; Holographic microscopy; Phase images; Membrane effect

Electroporation-based techniques are known for their potential to temporarily increase cells membrane permeability by controlled electric fields for transfer of non-permeant molecules; these techniques evolved in many useful biomedical applications. Current research in this domain addresses both experimental and computational analysis in a complementary manner. Numerical simulations, considering realistic cell shapes and field exposure conditions can complete the experimental investigations by opening insights and providing quantitative data. Our approach here provides cell models for EP simulations, based on experimental acquisition of images in a holographic microscopy setup and digital reconstruction of phase images of living attached B16F10 murine melanoma cells. A procedure to process and import phase images in dedicated finite element software COMSOL Multiphysics is described in detail. Based on such realistically shaped computational domains, the electric field problem is successively defined and solved under time-harmonic electric excitation, uniformly applied; the frequency dependent dielectric properties are set accordingly. Induced transmembrane voltage distribution is the representative numerical output of the analysis shown here for different expo sure conditions (membrane regions under stress, dielectric properties, field frequency), aiming to evaluate their potential efficiency on electroporation.

Article 42

An experimental system for real-time fluorescence recordings of cell membrane changes induced by electroporation

Ioan Tivig, Tudor Savopol, Eugenia Kovacs, Mihaela G Moisescu

Journal: European Biophysical Journal

Year: 2020

DOI: 10.1007/s00249-019-01417-9

3D prototyping; Electric field modeling; Electroporation; Generalized polarization; Real-time fluorescence recording.

     The electroporation of cells is nowadays used for a large variety of purposes, from basic research to cancer therapy and food processing. Understanding molecular mechanisms of the main processes involved in electroporation is thus of significant interest. In the present work, we propose an experimental system to record in real time the evolution of any cell parameter which can be evaluated by fluorescence (before, during and after application of the electroporation pulses to cells in suspension). The system is based on the design of adequate electroporation electrodes, compatible with a standard spectrofluorometer cuvette housing. The electric field intensity generated when pulses are applied was carefully characterized for different geometries of the electrodes, to choose a construction ensuring the greatest homogeneity of the field in combination with the best possible illumination of the sample. As an example of the method’s application, we present here generalized polarization kinetics for a varying number of electroporation pulses applied to a cell suspension; the general polarization parameter is strongly correlated to water presence in the hydrophobic membrane core. The system may be used for many other fluorescence measurements useful for the characterization of the electroporation process.

Article 41

Concentrations of Lead, Mercury, Arsenic, Cadmium, Manganese, and Aluminum in Blood of Romanian Children Suspected of Having Autism Spectrum Disorder

Manouchehr Hessabi, Mohammad H Rahbar, Iuliana Dobrescu, MacKinsey A Bach, Liana Kobylinska, Jan Bressler, Megan L Grove, Katherine A Loveland, Ilinca Mihailescu, Maria Cristina Nedelcu, Mihaela Georgeta Moisescu, Bogdan Mircea Matei, Christien Oktaviani Matei, Florina Rad 

Journal: International journal of environmental research and public health

Year: 2019

DOI: 10.3390/ijerph16132303 

Romania; Aluminum; Arsenic; Autism Spectrum disorder; Cadmium; Lead; Manganese; Mercury.

Environmental exposure to lead (Pb), mercury (Hg), arsenic (As), cadmium (Cd), manganese (Mn), and aluminum (Al) has been associated with neurodevelopmental disorders including autism spectrum disorder (ASD). We conducted a pilot study during May 2015-May 2107 to estimate blood concentrations of six metals (Pb, Hg, As, Cd, Mn, and Al) and identify their associated factors for children with ASD or suspected of having ASD in Romania. Sixty children, age 2-8 years, were administered versions of ADOS or ADI-R translated from English to Romanian. After assessment, 2-3 mL of blood was obtained and analyzed for the concentrations of the six metals. The mean age of children was 51.9 months and about 90% were male. More than half (65%) of the children were born in Bucharest. Over 90% of concentrations of As and Cd were below limits of detection. Geometric mean concentrations of Pb, Mn, Al, and Hg were 1.14 μg/dL, 10.84 μg/L, 14.44 μg/L, and 0.35 μg/L, respectively. Multivariable linear regression analysis revealed that children who were female, had less educated parents, exhibited pica, and ate cold breakfast (e.g., cereal), watermelon, and lamb had significantly higher concentrations of Pb compared to their respective referent categories (all p < 0.05 except for eating lamb, which was marginally significant, p = 0.053). Although this is the first study that provides data on concentrations of the six metals for Romanian children with ASD, the findings from this study could be useful for designing future epidemiologic studies for investigating the role of these six metals in ASD in Romanian children.

Article 40

Controlling drug release from mesoporous silica through an amorphous, nanoconfined 1-tetradecanol layer

Raul-Augustin Mitran, Cristian Matei, Daniela Berger, Laura Băjenaru, Mihaela G Moisescu

Journal: Antioxidants

Year: 2018

DOI: 10.1016/j.ejpb.2018.02.020

Controlled release; Drug delivery systems; Interfacial layer; Mesoporous silica; Tetradecanol

Mesoporous silica materials are promising nano-carriers for drug delivery systems. Even though there are many strategies for controlling the drug release kinetics, these must be adapted through trial and error on a case-by-case basis. Here we explore the possibility of tailoring the release kinetics of hydrophilic, water soluble therapeutic agents from mesoporous silica through addition of a hydrophobic excipient, 1-tetradecanol. In vitro drug release experiments performed at 37 °C, in phosphate buffer solution (pH 7.4) show that the addition of tetradecanol yields slower drug release kinetics, which was correlated with the presence of a liquid fatty alcohol interfacial layer. The layer mass is 11-23 wt.% of the metoprolol-loaded silica sample, and it causes up to 1.6 times decrease of initial release rate with respect to materials without the fatty alcohol. This effect does not depend of carrier pore arrangement, being noticed for both hexagonal MCM-41 and cubic KIT-5 mesoporous silica. The toxicity of tetradecanol-containing materials was evaluated by formazan-based viability assay on Opossum kidney epithelial cell line, and no significant toxicity was observed.

Article 39

Noninvasive detection of changes in cells' cytosol conductivity by combining dielectrophoresis with optical tweezers

Moisescu, Mihaela Georgeta; Savopol, Tudor; Dimitriu, Liviu; Cemazar, Jaka; Kovacs, Eugenia; Radu, Mihai

Journal: Analytica Chimica ACTA

Year: 2018

DOI: 10.1016/j.aca.2018.05.010  

 

Cytosol conductivity; Dielectrophoresis; Optical tweezers; Electroporation; Clausius-Mossotti factor; Murine melanoma cells

Cellular electrical properties are modulated by various physical and/or chemical stresses and detection of these changes is a challenging issue. Optical tweezers (OT) and dielectrophoresis (DEP) are frequently integrated to devices dedicated to the investigation of cells properties. Here we provide a technique to detect changes in cytosol conductivity of cells by using a combination of DEP and OT. The method was exemplified for the case of cells electroporation and is based on balancing the DEP force by a controlled OT force. We observed a decrease of the DEP force in the case of electroporated cells which was correlated to a decrease of cytosol conductivity by means of Clausius- Mossotti factor modeling. For highly stressing electroporation pulses, the cytosol conductivity drops to values close to those of the cells suspending medium. These results are consistent with those reported in the literature proving the robustness of our proposed sensing method. (C) 2018 Elsevier B.V. All rights reserved.

Article 38

Evaluation of the metastatic potential of malignant cells by image processing of digital holographic microscopy data

Violeta L Calin, Mona Mihailescu, Eugen I Scarlat, Alexandra V Baluta, Daniel Calin, Eugenia Kovacs, Tudor Savopol, Mihaela G. Moisescu

Journal: FEBS Open Bio

Year: 2017

DOI: 10.1002/2211-5463.12282

Bimodality coefficient analysis of quantitative phase image; Clonogenic test; Digital holographic microscopy; Impedance‐based cell proliferation test; Metastatic potential; Murine B16 malignant cells

The cell refractive index has been proposed as a putative cancer biomarker of great potential, being correlated with cell content and morphology, cell division rate and membrane permeability. We used digital holographic microscopy to compare the refractive index and dry mass density of two B16 murine melanoma sublines of different metastatic potential. Using statistical methods, the distribution of phase shifts within the reconstructed quantitative phase images was analyzed by the method of bimodality coefficients. The observed correlation of refractive index, dry mass density and bimodality profile with the metastatic potential of the cells was validated by real time impedance-based assay and clonogenic tests. We suggest that the refractive index and bimodality analysis of quantitative phase image histograms could be developed as optical biomarkers useful in label-free detection and quantitative evaluation of cell metastatic potential.

Article 36

Changes in optical properties of electroporated cells as revealed by digital holographic microscopy

Violeta L Calin, Mona Mihailescu, Nicolae Mihale, Alexandra V. Baluta, Eugenia Kovacs, Tudor Savopol, Mihaela G. Moisescu

Journal: Biomedical Optics Express

Year: 2017

DOI: 10.1364/BOE.8.002222 

Digital holography; Medical optics and biotechnology; Cell analysis

Changes in optical and shape-related characteristics of B16F10 cells after electroporation were investigated using digital holographic microscopy (DHM). Bipolar rectangular pulses specific for electrochemotherapy were used. Electroporation was performed in an “off-axis” DHM set-up without using exogenous markers. Two types of cell parameters were monitored seconds and minutes after pulse train application: parameters addressing a specifically defined area of the cell (refractive index and cell height) and global cell parameters (projected area, optical phase shift profile and dry mass). The biphasic behavior of cellular parameters was explained by water and mannitol dynamics through the electropermeabilized cell membrane.

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