Flexible Triboelectric Nanogenerator for Promoting the Proliferation and Migration of Human Fibroblast Cells.

Chronic wound healing is often a prolonged process with the migration and proliferation of fibroblast cells playing crucial roles. Electrical stimulation (ES) has emerged as a promising physical therapy modality to promote these key events. In this study, we address this issue by employing a triboelectric nanogenerator (TENG) as an electrical stimulator for both drug release and the stimulation of fibroblast cells. The flexible TENG with a sandwich structure was fabricated using a PCL nanofibrous layer, Kapton, and silicon rubber. The TENG could be folded to any degree and twisted, and it could return to its original shape when the force was removed. Cultured cells received ES twice and three times daily for 8 days, with a 30 min interval between sessions. By applying current in a safe range and appropriate time (twice daily), fibroblasts demonstrate an accelerated proliferation and migration rate. These observations were confirmed through cell staining. Additionally, in vitro tests demonstrated the TENG's ability to simultaneously provide ES and release vitamin C from the patch. After 2 h, the amount of released drug increased 2 times in comparison to the control group. These findings provide support for the development of a TENG for the treatment of wounds, which underlines the promise of this new technique for developing portable electric stimulation devices.

Computational modeling of the variation of the transmembrane potential of the endothelial cells of the blood-brain-barrier subject to an external electric field.

The electromechanical properties of the membrane of endothelial cells forming the blood-brain barrier play a vital role in the function of this barrier. The mechanical effect exerted by external electric fields on the membrane could change its electrical properties. In this study the effect of extremely low frequency (ELF) external electric fields on the electrical activity of these cells has been studied by considering the mechanical effect of these fields on the capacitance of the membrane. The effect of time-dependent capacitance of the membrane is incorporated in the current components of the parallel conductance model for the electrical activity of the cells. The results show that the application of ELF electric fields induces hyperpolarization, having an indirect effect on the release of nitric oxide from the endothelial cell and the polymerization of actin filaments. Accordingly, this could play an important role in the permeability of the barrier. Our finding can have possible consequences in the field of drug delivery into the central nervous system.

Density functional theory computation of the intermolecular interactions of Al2@C24 and Al2@Mg12O12 semiconducting quantum dots conjugated with the glycine tripeptide.

The nature of intermolecular forces within semiconductor quantum dot systems can determine various physicochemical properties, as well as their functions, in nanomedical applications. The purpose of this study has been to investigate the nature of the intermolecular forces operating between Al2@C24 and Al2@Mg12O12 semiconducting quantum dots and the glycine tripeptide (GlyGlyGly), and also consider whether permanent electric dipole-dipole interactions play a significant role vis-à-vis these molecular systems. The energy computations, including the Keesom and the total electronic interactions and the energy decomposition, together with the quantum topology analyses were performed. Our results demonstrate that no significant correlation is found between the magnitude and orientation of the electrical dipole moments, and the interaction energy of the Al2@C24 and Al2@Mg12O12 with GlyGlyGly tripeptide. The Pearson correlation coefficient test revealed a very weak correlation between the quantum and the Keesom interaction energies. Apart from the quantum topology analyses, the energy decomposition consideration confirmed that the dominant share of the interaction energies was associated with the electrostatic interactions, yet both the steric and the quantum effects also made appreciable contributions. We conclude that, beside the electrical dipole-dipole interactions, other prominent intermolecular forces, such as the polarization attraction, the hydrogen bond, and the van der Waals interactions can also influence the interaction energy of the system. The findings of this study can be utilized in several areas in the field of nanobiomedicine, including the rational design of cell-penetrating and intracellular drug delivery systems using semiconducting quantum dots functionalized with a peptide.

Enhanced proliferation and migration of fibroblast cells by skin-attachable and self-cleaning triboelectric nanogenerator.

Skin wounds are common in accidental injuries, surgical operations, and chronic diseases. The migration and proliferation of fibroblast cells are fundamental to wound healing, which can be promoted by electrical stimulation as a physical therapy modality. Therefore, the development of portable electrical stimulation devices that can be used by patients on-site is an essential need. In the present study, a self-cleaning triboelectric nanogenerator (TENG) has been fabricated for enhancing cell proliferation and migration. The polycaprolactone­titanium dioxide (PCL/TiO2) and polydimethylsiloxane (PDMS) layers were fabricated via a facile method and used as the electropositive and electronegative pair, respectively. The effect of stimulation time on proliferation and migration of fibroblast cells was investigated. The results demonstrated that when the cells were stimulated once-a-day for 40 min, the cell viability was increased, while a long daily stimulation time has an inhibitory effect. Under electrical stimulation, the cells move toward the middle of the scratch, making the scratch almost invisible. During repeated movements, the prepared TENG connected to a rat skin generated an open-circuit voltage and a short-circuit current around 4 V and 0.2 µA, respectively. The proposed self-powered device can pave the way for a promising therapeutic strategy for patients with chronic wounds.

Shortening the sulfur cell cycle by a green approach for bio-production of extracellular metalloid-sulfide nanoparticles.

In the present study, a new approach was introduced regarding the extracellular synthesis of selenium sulfide micro/nano-particles using Saccharomyces cerevisiae in different ammonium sulfate supplementation and in the presence of sodium selenosulfate precursors (S1) and a blend of selenous acid and sodium sulfite (S2). In S1, only cell supernatant exposed to ammonium sulfate was able to reduce sodium selenosulfate. Whereas, in S2, cell supernatant in both pre-conditions of with or without ammonium sulfate (S2 + or S2-) were able to reduce selenous acid and sodium sulfite. Electron microscopy, also indicated that selenium sulfide NPs were successfully synthesized with average size of 288 and 332 nm for S2 + and S2- in SEM and 268 and 305 nm in TEM. Additionally, elemental mapping by energy-dispersive x-ray analysis confirmed the presence of sulfur/selenium elements in the particles in a proportion of 24.50 and 23.31 for S2- and S2 + , respectively. The mass spectrometry indicated the probability of Se2S2, SeS1.1, Se2, Se, SeS5, SeS3, Se3S5/Se5, Se3/SeS5, Se6, Se4/SeS7, Se2.57S5.43/Se2S2 and Se4S/Se2S6 molecules for S2 + and of Se, Se2, Se3S5/Se5, Se6 and Se4 species for S2-. In FTIR spectra, primary (i.e. 1090-1020 and 1650-1580 cm-1) and secondary (1580-1490 cm-1) amine bands duly confirmed the protein corona around the NPs.

Deflection-based laser sensing platform for selective and sensitive detection of H2S using plasmonic nanostructures.

Considering the severe hazards of abnormal concentration level of H2S as an extremely toxic gas to the human body and due to the disability of olfactory system in sensing toxic level of H2S concentration, a reliable, sensitive, selective and rapid method for the detection of H2S is proposed and its efficacy is analyzed through simulation. The proposed system is based on the deflection of a laser beam in response to the temperature variations in its path. In order to provide selectivity and improve sensitivity, gold nanostructures were employed in the system. The selectivity was introduced based on the thiol-gold interactions and the sensitivity of the system was enhanced due to the modification of plasmon resonance behavior of gold nanostructures in response to gas adsorption. Results from our analysis demonstrate that compared with Au and SiO2-Au, the Au nanomatryoshka structures (Au-SiO2-Au) showed the highest sensitivity due to promoting higher deflections of the laser beam.

A computational modelling study of excitation of neuronal cells with triboelectric nanogenerators.

Neurological disorders and nerve injuries, such as spinal cord injury, stroke, and multiple sclerosis can result in the loss of muscle function. Electrical stimulation of the neuronal cells is the currently available clinical treatment in this regard. As an effective energy harvester, the triboelectric nanogenerators (TENG) can be used for self-powered neural/muscle stimulations because the output of the TENG provides stimulation pulses for nerves. In the present study, using a computational modelling approach, the effect of surface micropatterns on the electric field distribution, induced voltage and capacitance of the TENG structures have been investigated. By incorporating the effect of the TENG inside the mathematical model of neuron's electrical behavior (cable equation with Hodgkin-Huxley model), its impact on the electrical behavior of the neurons has been studied. The results show that the TENG operates differently with various surface modifications. The performance of the TENG in excitation of neurons depends on the contact and release speed of its electrodes accordingly.

A modeling study of the effect of an alternating magnetic field on magnetite nanoparticles in proximity of the neuronal microtubules: A proposed mechanism for detachment of tau proteins.

BACKGROUND AND OBJECTIVE: It is known that the disintegration of microtubules in neurons occurs in response to the phosphorylation of the tau proteins that promotes the structural instability of the microtubules, as one of the factors underlying the onset of Alzheimer's disease (AD). METHODS: In this study, the mechanical variations undergone by the tau protein's and microtubule's structures due to the action of intrinsic magnetite nanoparticles inside the brain tissue have been computationally modeled using the finite element (FEM) method. RESULTS: The von Mises stress induced by magnetite nanoparticles, subject to an applied alternating magnetic field, leads to local heating and mechanical forces, prompting a corresponding deformation in, and displacement of, the microtubule and the tau protein. CONCLUSIONS: The induction of these deformations would increase the probability of the microtubules' depolymerization, and hence their eventual structural disintegration.

The investigation into the effect of the length of RGD peptides and temperature on the interaction with the αIIbß3 integrin: a molecular dynamic study.

The tripeptide Arg-Gly-Asp acid (RGD) is a protein sequence in the binding of proteins to cell surfaces, and is involved in various biological processes such as cell adhesion to the extracellular matrix, platelet activation, hemostasis, etc. The C2 domain of the Von Willebrand Factor (VWF), containing the RGD motif, plays an important role in the initial homeostasis process. It binds to the αIIbß3 integrin and stimulates platelet aggregation. We have investigated, using the molecular Dynamic (MD) simulation method, the effect of the RGD-peptide length, and temperature variation, on the binding to the αIIbß3 integrin receptor. We examined 10 different structural modes of the αIIbß3 at three different temperatures; 237 K, 310 K and 318 K. Our findings show that the amino acids that form a binding pocket include Asp224, Tyr234, Ser226, Tyr190, Tyr189, Trp260, Trp262, Asp259, Lys253, Arg214, Asp217, Ser161 and Ala218 and that the ligand-receptor interaction was increased at higher temperatures. It was also found that the increase in the number of ligands' amino acids and their types (% glycine) plays an important role in the stability, conformation, and ligand-receptor interaction.Communicated by Ramaswamy H. Sarma.

A proposed implantable voltammetric carbon fiber-based microsensor for corticosteroid monitoring by cochlear implants.

A novel carbon fiber microsensor (CFMS) with the capability of being inserted in the cochlear implant structure is introduced for in situ measurement of corticosteroid concentration. The microsensor structure is composed of a carbon microfiber, an Ag wire, and a Pt wire acting respectively as a working electrode, a reference electrode, and a counter electrode. In addition, a silicone septum is used for isolation purposes in place of the epoxy resin. The septum-insulated microsensor is capable of monitoring the concentration of the corticosteroids in the perilymph fluid without a need for sampling from the inner ear fluid and the consequent ex vivo analysis. The electrochemical determination of the corticosteroids was investigated on the carbon fiber electrode surface by differential pulse voltammetry. During the reduction of dexamethasone (DEX), a cathodic peak with a peak potential of -1.3 V appeared at the CFMS. Using the CFMS under optimized conditions, a calibration plot of the dexamethasone (DEX) in the artificial perilymph solution exhibited two linear ranges from 10 nM to 2 µM and 2 to 40 µM (sensitivity equal to 16.55 µA µM-1 cm-2; LOD = 4 nM) conforming with the DEX concentration range inside the inner ear after the insertion of a drug-eluting cochlear implant electrode (CIE). Furthermore, the interferences occurring in the hearing functions of the CIE after the presence and function of the CFMS were simulated numerically using the finite element method. According to our results, decreasing the size of the microsensor introduces lower interferences with the auditory function of the cochlear implant electrode.

Determination of the optimal location of samples on quartz tuning fork-based biosensors: a computational study.

In view of efficiency, simple operation, and affordable cost and disposability, quartz tuning fork systems form good candidates for mechanical-based biosensors in point of care applications. Based on the geometrical structure, the frequency response of the tuning fork- based sensors is dependent on the location of absorbed samples. In order to have the maximum efficiency and sensitivity, the optimized condition of sample loading on the fork structures should be considered. In this regard, here, we have determined the optimized sample location to be on the prongs of the quartz tuning fork by calculating the frequency response of the quartz tuning fork using the finite element method. From an application point of view, we have obtained an agreement between the calculational method and the experimental excitation technique of the structure. The results from our study show that by using an appropriate location for the sample, the quartz tuning fork could be exploited with high sensitivity.

Population Kinetics and Mechanistic Aspects of Saccharomyces cerevisiae Growth in Relation to Selenium Sulfide Nanoparticle Synthesis.

Biosynthesis of nanoparticles (NPs) by microorganisms is a cost- and energy-effective approach. However, how the production of NPs affects the population of producing organism remains as an unresolved question. The present study aimed to evaluate the kinetics of Saccharomyces cerevisiae growth in relation to synthesis of selenium sulfide nanoparticles by using a population model. To this end, the population of S. cerevisiae cells was investigated in terms of colony forming units (CFU) in the presence of the substrate in different time points. Fluctuation of sulfite reductase (SiR) activity, expression of MET5 and MET10 genes, and concentrations of sulfite and selenium were evaluated to support the population findings. CFU values in the test groups were lower than those in the control counterparts. The rise and fall of the SiR activity and MET5 and MET10 gene expression conformed to the variations of CFU values. The rate of reduction in the selenium and sulfite concentrations tended to decrease over the time. In conclusion, the cells population was negatively and positively affected by selenium and sulfite concentrations, respectively. The indirect relationship of the selenium ions concentration in the path analysis revealed that the product, selenium sulfide nanoparticles, caused this drop in S. cerevisiae cells population.

Computational modeling to determine key regulators of hypoxia effects on the lactate production in the glycolysis pathway.

In solid tumors, hypoxia can trigger aberrant expression of transcription factors and genes, resulting in abnormal biological functions such as altered energetic pathways in cancer cells. Glucose metabolism is an important part of this phenomenon, which is associated with changes in the functional expression of transporters and enzymes involved in the glycolysis pathway. The latter phenomenon can finally lead to the lactate accumulation and pH dysregulation in the tumor microenvironment and subsequently further invasion and metastasis of cancer cells. Having capitalized on the computational modeling, in this study, for the first time, we aimed to investigate the effects of hypoxia-induced factor-1 (HIF-1) mediated hypoxia on the magnitude of functional expression of all the enzymes and transporters involved in the glycolysis process. The main objective was to establish a quantitative relationship between the hypoxia intensity and the intracellular lactate levels and determine the key regulators of the glycolysis pathway. This model clearly showed an increase in the lactate concentration during the oxygen depletion. The proposed model also predicted that the phosphofructokinase-1 and phosphoglucomutase enzymes might play the most important roles in the regulation of the lactate production.

Phototherapy alters the oncogenic metabolic activity of breast cancer cells.

BACKGROUND: Metabolic reprogramming in cancer cells is a strategy to attain a high proliferation rate, invasion, and metastasis. In this study, the effects of phototherapy at different wavelengths were investigated on the metabolic activity of breast cancer cells. METHODS: The states of the MCF7 cells proliferation and viability were measured by the MTT assay. Glucose consumption and the lactate formation in the LED-irradiated cells culture were analyzed by biochemical assay kits. The Amino acid concentration in the culture media of the MCF7 cells was analyzed using HPLC. Moreover, the gene expression of some glycolytic, TCA cycle and pentose phosphate cycleenzymes were assessed by real time PCR. RESULTS: Phototherapy at wavelength of 435 nm decreased the cell viability by 23 % when the energy dose was 17.5 J/cm2 compared to the control group. The expression of the LDHA and GLS was up-regulated in 629 nm-treated cells while the expression of these genes was down-regulated in the MCF7 cells irradiated at 435 nm in comparison with the control group. Consequently, the glucose consumption and the lactate formation were diminished respectively by 22 % and 15 % in the 435 nm-irradiated cells while the glucose consumption and the lactate formation were increased in the 629 nm-irradiated cells by 112 % and 107 % in comparison with the control group. In addition, the analysis of the glutamine concentration by the HPLC indicated that the blue light irradiation decreased the glutamine consumption while the red light increased it in comparison with the control group.

Enhancement of the biological autoluminescence by mito-liposomal gold nanoparticle nanocarriers.

One of the most important barriers to the detection of the biological autoluminescence (BAL) from biosystems using a non-invasive monitoring approach, in both the in vivo and the in vitro applications, is its very low signal intensity (< 1000 photons/s/cm2). Experimental studies have revealed that the formation of electron excited species, as a result of reactions of biomolecules with reactive oxygen species (ROS), is the principal biochemical source of the BAL which occurs during the cell metabolism. Mitochondria, as the most important organelles involved in oxidative metabolism, are considered to be the main intracellular BAL source. Hence, in order to achieve the BAL enhancement via affecting the mitochondria, we prepared a novel mitochondrial-liposomal nanocarrier with two attractive features including the intra-liposomal gold nanoparticle synthesizing ability and the mitochondria penetration capability. The results indicate that these nanocarriers (with the average size of 131.1 ±â€¯20.1 nm) are not only able to synthesize the gold nanoparticles within them (with the average size of 15 nm) and penetrate into the U2OS cell mitochondria, but they are also able to amplify the BAL signals. Our results open new possibilities for the use of biological autoluminescence as a non-invasive and label-free monitoring method in nanomedicine and biotechnology.

Amperometric lactate nanobiosensor based on reduced graphene oxide, carbon nanotube and gold nanoparticle nanocomposite.

A sensitive amperometric method is reported for the determination of lactate. A platinum electrode was modified with a composite prepared from reduced graphene oxide (rGO), carbon nanotubes (CNTs) and gold nanoparticles. The composite was synthesized by the in-situ reduction of gold(III) ions on the GO-CNT hybrid. Triple composite components showed synergistic effects on the enzyme loading, electrocatalytic activity and electron transfer between receptor and electrode surface. The amperometric lactate sensor was obtained by immobilization of lactate oxidase (LOx) on the modified electrode. LOx catalyzes the conversion of lactate into pyruvate and hydrogen peroxide. The generated hydrogen peroxide is simultaneously involved in the oxidation reaction, which is associated with the electron production. These electrons act as amperometric signal generators. At the low potential of 0.2 V, the nanobiosensor shows a relatively wide linear analytical range (i.e., 0.05-100 mM of lactate) with high electrochemical sensitivity (35.3 µA mM-1 cm-2) and limit of detection of 2.3 µM. The sensor is stable, repeatable and reproducible. It is a highly sensitive tool for the detection of lactate in biological samples under both normoxic and hypoxic conditions. Graphical abstract Schematic representation of an electrochemical biosensor for sensitive detection of lactate in biological and food samples based on reduced graphene oxide-carbon nanotube-gold nanocomposite, as a surface modifier, and lactate oxidase, as a bioreceptor.

Electrochemical Determination of Dexamethasone by Graphene Modified Electrode: Experimental and Theoretical Investigations.

We report on a combined experimental and theoretical study concerning the electrochemical behavior of the dexamethasone (DEX) on a graphene modified glassy carbon electrode (GCE). A good agreement between experiments and density functional theory (DFT)-based calculations is observed for the DEX reduction. The electrochemical behavior of the DEX was investigated on the surface of a glassy carbon electrode (GCE) modified with different type of graphenes, including graphene quantum dot (GQD), graphene oxide (GO), electrochemically synthesized graphene (EG), graphene synthesized by the Hummer method (HG) and graphene nanoplate (GNP) using voltammetric techniques (CV, DPV and SWV). The results exhibited a significant increase in the reduction of the peak current of the DEX in  the GNP modified GCE (GNP/GCE) in comparison to other modified electrodes and bare GCE. The unique morphology, size and electro catalytic properties of the GNP cause a sensitive response of the DEX in a novel sensor. Under the optimized experimental condition, the GNP/ GCE showed two linear dynamic ranges of 0.1-50 µM and 50-5000 µM with a low detection limit of 15 nM for determination of the DEX. The novel sensor is successfully applied to the sensitive determination of the DEX in human plasma samples with satisfactory recoveries. Energy of the LUMO and HUMO orbitals and energy calculations for the DEX molecule interacting with graphene were performed using the density functional B3LYP/6-31G. The theoretical results allied to significant charge transfer took place due to the interaction of the DEX with the applied graphene.

Physicochemical properties, antifungal activity and cytotoxicity of selenium sulfide nanoparticles green synthesized by Saccharomyces cerevisiae.

Selenium sulfide is a well-known bioactive chemical whose biosynthesis as a nanoparticle (NP) is a controversial issue. In the present study, we employed Saccharomyces cerevisiae to generate a novel synthetic process of selenium sulfide NPs. The addition of selenium/sulfur precursors to S. cerevisiae culture produced NPs, which we isolated and characterized the physicochemical properties, toxicity, and antifungal activity. Transmission electron microscopy indicated the presence of the NPs inside the cells. Selenium sulfide NPs were successfully synthesized with average size of 6.0 and 153 nm with scanning electron micrographs and 360 and 289 nm in Zeta sizer using different precursors. The presence of sulfur/selenium in the particles was confirmed by energy-dispersive X-ray spectroscopy and elemental mapping. Fourier-transform infrared spectroscopy supported the production of selenium sulfide NPs. X-ray diffractograms showed the presence of characteristic peaks of selenium sulfide NPs which were further confirmed by mass spectrometry. The obtained NPs strongly inhibited the growth of pathogenic fungi that belonged to the genera Aspergillus, Candida, Alternaria and the dermatophytes, while no cytotoxicity was observed in MTT assay. In conclusion, efficient green synthesis of selenium sulfide NPs with appropriate physicochemical properties is possible in bio-systems like S. cerevisiae.

Synergistic effect of phototherapy and chemotherapy on bladder cancer cells.

Drug resistance as an important barrier to cancer treatment, has a close relation with alteration of cancer metabolism. Therefore, in this study the synergistic effect of phototherapy and chemotherapy were investigated on the bladder cancer cells viability. The cytotoxicity effect of blue light irradiation was measured by the MTT assay. Glucose consumption, lactate and ammonium formation were analyzed in the blue LED-irradiated cancer cells culture. Also, the expression of some genes involved in apoptosis and epithelial-mesenchymal transition was assessed using real-time PCR in comparison with the control group. The analysis of the results indicated that blue light irradiation inhibited the cell viability in a dose-dependent manner. Blue light irradiation decreased the cell viability by 7% and 19% (p < .05) in 5637 cells at doses of 8.7 J/cm2 and 17.5 J/cm2 in comparison with the control group respectively. Glucose consumption, lactate and ammonium formation diminished in the blue LED-irradiated 5637 cells in both doses. The real time PCR results indicated that the expression of Bax increased in blue light-irradiated cells. In addition, the cell cycle analysis showed that blue light irradiation arrested the bladder cancer in the G1 phase. Also, the effect of combination therapy on cancer cells was investigated in presence of blue light irradiation and cisplatin. The obtained results of the MTT assay indicated that blue light irradiation enhance the cytotoxicity effect of cisplatin on bladder cancer cells.