Two‐dimensional polynomial type canonical relaxation oscillator model for p53 dynamics

p53 network, which is responsible for DNA damage response of cells, exhibits three distinct qualitative behaviours; low state, oscillation and high state, which are associated with normal cell cycle progression, cell cycle arrest and apoptosis, respectively. The experimental studies demonstrate that these dynamics of p53 are due to the ATM and Wip1 interaction. This paper proposes a simple two‐dimensional canonical relaxation oscillator model based on the identified topological structure of ATM and Wip1 interaction underlying these qualitative behaviours of p53 network. The model includes only polynomial terms that have the interpretability of known ATM and Wip1 interaction. The introduced model is useful for understanding relaxation oscillations in gene regulatory networks. Through mathematical analysis, we investigate the roles of ATM and Wip1 in forming of these three essential behaviours, and show that ATM and Wip1 constitute the core mechanism of p53 dynamics. In agreement with biological findings, we show that Wip1 degradation term is a highly sensitive parameter, possibly related to mutations. By perturbing the corresponding parameters, our model characterizes some mutations such as ATM deficiency and Wip1 overexpression. Finally, we provide intervention strategies considering our observation that Wip1 seems to be an important target to conduct therapies for these mutations.Inspec keywords: enzymes, molecular biophysics, molecular configurations, genetics, cellular biophysicsOther keywords: two‐dimensional polynomial type canonical relaxation oscillator model, p53 dynamics, p53 network, gene regulatory network, DNA damage response, normal cell cycle progression, cell cycle arrest, cell apoptosis, ATM interaction, Wip1 interaction, ataxia‐telangiectasia mutated interaction, wild‐type p53‐induced phosphatase 1 interaction, topological structure, mathematical analysis     

Coupling of cell fate selection model enhances DNA damage response and may underlie BE phenomenon

Double‐strand break‐induced (DSB) cells send signal that induces DSBs in neighbour cells, resulting in the interaction among cells sharing the same medium. Since p53 network gives oscillatory response to DSBs, such interaction among cells could be modelled as an excitatory coupling of p53 network oscillators. This study proposes a plausible coupling model of three‐mode two‐dimensional oscillators, which models the p53‐mediated cell fate selection in globally coupled DSB‐induced cells. The coupled model consists of ATM and Wip1 proteins as variables. The coupling mechanism is realised through ATM variable via a mean‐field modelling the bystander signal in the intercellular medium. Investigation of the model reveals that the coupling generates more sensitive DNA damage response by affecting cell fate selection. Additionally, the authors search for the cause‐effect relationship between coupled p53 network oscillators and bystander effect (BE) endpoints. For this, they search for the possible values of uncertain parameters that may replicate BE experiments’ results. At certain parametric regions, there is a correlation between the outcomes of cell fate and endpoints of BE, suggesting that the intercellular coupling of p53 network may manifest itself as the form of observed BEs.Inspec keywords: biological effects of ionising particles, molecular biophysics, biochemistry, DNA, cellular biophysics, physiological models, biomolecular effects of radiation, cellular effects of radiation, biological effects of X‐rays, oscillations, proteinsOther keywords: three‐mode two‐dimensional oscillators, p53‐mediated cell fate selection, globally coupled DSB‐induced cells, coupled model consists, coupling mechanism, ATM variable, bystander signal, intercellular medium, sensitive DNA damage response, coupled p53 network oscillators, intercellular coupling, cell fate selection model, double‐strand break‐induced cells, DSBs, neighbour cells, oscillatory response, excitatory coupling, plausible coupling model     

Contribution of time delays to p53 oscillation in DNA damage response

Although the oscillatory dynamics of the p53 network have been extensively studied, the understanding of the mechanism of delay‐induced oscillations is still limited. In this paper, a comprehensive mathematical model of p53 network is studied, which contains two delayed negative feedback loops. By studying the model with and without explicit delays, the results indicate that the time delay of Mdm2 protein synthesis can well control the pulse shape but cannot induce p53 oscillation alone, while the time delay required for Wip1 protein synthesis induces a Hopf bifurcation to drive p53 oscillation. In addition, the synergy of the two delays will cause the p53 network to oscillate in advance, indicating that p53 begins the repair process earlier in the damaged cell. Furthermore, the stability and bifurcation of the model are addressed, which may highlight the role of time delay in p53 oscillations.Inspec keywords: proteins, cellular biophysics, DNA, molecular biophysics, biomolecular effects of radiation, bifurcation, physiological models, cellular effects of radiation, oscillations, geneticsOther keywords: highlight, time delay, delayed negative feedback loops, murine double minute 2, Wip1 protein synthesis, explicit delays, Mdm2 protein synthesis, p53 network     

Oscillation induced by Hopf bifurcation in the p53–Mdm2 feedback module

This study develops an integrated model of the p53–Mdm2 interaction composed of five basic components and time delay in the DNA damage response based on the existing research work. Some critical factors, including time delay, system parameters, and their interactions in the p53–Mdm2 system are investigated to examine their effects on the oscillatory behaviour induced by Hopf bifurcation. It is shown that the positive feedback formed between p53 and the activity of Mdm2 in the cytoplasm can cause a slight decrease in the amplitude of the p53 oscillation. The length of the time delay plays an important role in determining the amplitude and period of the oscillation and can significantly extend the parameter range for the system to demonstrate oscillatory behaviour. The numerical simulation results are found to be in good agreement with the published experimental observation. It is expected that the results of this research would be helpful to better understand the biological functions of p53 pathway and provide some clues in the treatment of cancer.Inspec keywords: numerical analysis, physiological models, molecular biophysics, feedback, DNA, bifurcation, proteins, delays, cancer, oscillations, cellular biophysicsOther keywords: Hopf bifurcation‐induced oscillations, p53–Mdm2 feedback mechanism, integrated model, p53–Mdm2 interaction, basic components, time delay, DNA damage response, existing research work, critical factors, system parameters, p53–Mdm2 system, oscillatory behaviour, positive feedback, parameter range     

System‐based strategies for p53 recovery

The authors have proposed a systems theory‐based novel drug design approach for the p53 pathway. The pathway is taken as a dynamic system represented by ordinary differential equations‐based mathematical model. Using control engineering practices, the system analysis and subsequent controller design is performed for the re‐activation of wild‐type p53. p53 revival is discussed for both modes of operation, i.e. the sustained and oscillatory. To define the problem in control system paradigm, modification in the existing mathematical model is performed to incorporate the effect of Nutlin. Attractor point analysis is carried out to select the suitable domain of attraction. A two‐loop negative feedback control strategy is devised to drag the system trajectories to the attractor point and to regulate cellular concentration of Nutlin, respectively. An integrated framework is constituted to incorporate the pharmacokinetic effects of Nutlin in the cancerous cells. Bifurcation analysis is also performed on the p53 model to see the conditions for p53 oscillation.Inspec keywords: proteins, tumours, cancer, cellular biophysics, molecular biophysics, molecular configurations, biochemistry, differential equations, closed loop systems, bifurcation, biology computingOther keywords: system‐based strategies, p53 recovery, systems theory‐based novel drug design approach, dynamic system, ordinary differential equations‐based mathematical model, control engineering practices, subsequent controller design, wild‐type p53, p53 revival, oscillatory, control system paradigm, mathematical model, Nutlin effect, attractor point analysis, domain‐of‐attraction, two‐loop negative feedback control strategy, cellular concentration, pharmacokinetic effects, cancerous cells, bifurcation analysis, p53 oscillation, anomalous cell     

Controllable synthesis and characterisation of palladium (II) anticancer complex‐loaded colloidal gelatin nanoparticles as a novel sustained‐release delivery system in cancer therapy

Over the past few years, there have been several attempts to deliver anticancer drugs into the body. It has been shown that compared to other available carriers, colloidal gelatin nanoparticles (CGNPs) have distinct properties due to their exceptional physico‐chemical and biological characteristics. In this study, a novel water‐soluble palladium (II) anticancer complex was first synthesised, and then loaded into CGNPs. The CGNPs were synthesised through a two‐step desolvation method with an average particle size of 378 nm. After confirming the stability of the drug in the nanoparticles, the drug‐loaded CGNPs were tested for in vitro cytotoxicity against human breast cancer cells. The results showed that the average drug encapsulating efficiency and drug loading of CGNPs were 64 and 10 ± 2.1% (w/w), respectively. There was a slight shift to higher values of cumulative release, when the samples were tested in lower pH values. In addition, the in vitro cytotoxicity test indicated that the number of growing cells significantly decreased after 48 h in the presence of different concentrations of drug. The results also demonstrated that the released drug could bind to DNA by a static mechanism at low concentrations (0.57 µM) on the basis of hydrophobic and hydrogen binding interactions.Inspec keywords: cancer, drug delivery systems, drugs, palladium compounds, colloids, gelatin, nanoparticles, nanomedicine, biomedical materials, nanofabrication, nanocomposites, molecular biophysics, molecular configurations, pH, solubility, particle size, cellular biophysics, encapsulation, DNA, hydrophobicity, hydrogen bondsOther keywords: controllable synthesis, sustained‐release delivery system, cancer therapy, palladium (II) anticancer complex‐loaded colloidal gelatin nanoparticles, anticancer drug delivery, physicochemical characteristics, biological characteristics, therapeutic pathways, water‐soluble palladium (II) anticancer complex, two‐step desolvation method, particle size, drug stability, gelatin matrix, drug‐loaded CGNPs, in vitro cytotoxic activity, human breast cancer cells, average drug encapsulating efficiency, pH values, cell growth, drug concentrations, DNA, static mechanism, hydrophobic interaction, hydrogen binding interactions     

Recovery of valuable metals from waste printed circuit boards using organic acids synthesised by Aspergillus niveus

Organic acids such as citric acid, itaconic acid and oxalic acid synthesised by Aspergillus niveus were used for the bioleaching of metals from waste printed circuit boards. Bioleaching of valuable metals was performed in one‐step, two‐steps and spent medium approaches using A. niveus. In the absence of waste printed circuit boards (WPCBs), the dry cell weight of A. niveus was higher when compared with the presence of WPCBs. Variations in the dry cell weight were observed for the presence of different particle sizes. The increase in itaconic acid and oxalic acid synthesis was found at a reduced particle size (60–80 mesh) and reached the maximum titre of itaconic acid (22.35 ± 0.87 mM) and oxalic acid (12.75 ± 0.54 mM) in 12 days during the two‐step bioleaching. The maximum recovery of 75.66% Zn, 73.58% Ni and 80.25% Cu from WPCBs was achieved in 15 days in two‐step leaching with particle sizes of the mesh being 60–80.     

Preparation of alginate oligosaccharide nanoliposomes and an analysis of their inhibitory effects on Caco‐2 cells

The conditions were optimised for preparing Alginate oligosaccharide (AOS) nanoliposomes, and Caco‐2 cell experiments were carried out to examine their antitumour effects. The optimal formulation of AOS nanoliposomes was as follows: a phosphatidylcholine‐to‐cholesterol ratio of 5.12, AOS concentration of 8.44 mg/mL, Tween 80 concentration of 1.11%, and organic phase to aqueous phase ratio of 5.25. Under the above conditions, the experimental encapsulation efficiency was 65.84%, and the AOS nanoliposomes exhibited a small particle size of 323 nm. After Caco‐2 cells were treated with AOS liposomes and AOS for 24 h, AOS nanoliposomes inhibited the growth of Caco‐2 cells to a greater extent than AOS at concentrations of 0.0625, 0.125, 0.25, 0.5 and 1 mg/mL (P  <  0.01). LDH leakage exhibited a concentration‐dependent increase following treatment with 0.5‐1 mg/mL AOS nanoliposomes, and the inhibitory effect of AOS nanoliposomes exhibited a more significant difference than AOS (P  <  0.01). Cells treated with 0.5 mg/mL and 1 mg/mL AOS nanoliposomes displayed a substantial and significant increase in activity compared with AOS (P  < 0.01). Based on these results, AOS nanoliposomes exerted a more significant effect on inhibiting Caco‐2 cell proliferation than AOS.Inspec keywords: evaporation, cellular biophysics, biomedical materials, biomembranes, nanomedicine, enzymes, biochemistry, drug delivery systems, particle size, response surface methodology, molecular biophysics, encapsulation, drugs, lipid bilayers, nanofabrication, materials preparation, polymers, nanostructured materialsOther keywords: reverse‐phase evaporation method, response surface methodology, alginate oligosaccharide nanoliposomes, mitochondrial function, AOS concentration, AOS liposomes, Caco‐2 cell proliferation, AOS nanoliposomes, methyl thiazolyl tetrazolium assay, cell counting kit‐8, lactate dehydrogenase, LDH assay, phosphatidylcholine‐to‐cholesterol ratio, size 323.0 nm, time 24.0 hour     

Non‐linear feedback control of the p 53 protein–mdm 2 inhibitor system using the derivative‐free non‐linear Kalman filter

It is proven that the model of the p 53–mdm 2 protein synthesis loop is a differentially flat one and using a diffeomorphism (change of state variables) that is proposed by differential flatness theory it is shown that the protein synthesis model can be transformed into the canonical (Brunovsky) form. This enables the design of a feedback control law that maintains the concentration of the p 53 protein at the desirable levels. To estimate the non‐measurable elements of the state vector describing the p 53–mdm 2 system dynamics, the derivative‐free non‐linear Kalman filter is used. Moreover, to compensate for modelling uncertainties and external disturbances that affect the p 53–mdm 2 system, the derivative‐free non‐linear Kalman filter is re‐designed as a disturbance observer. The derivative‐free non‐linear Kalman filter consists of the Kalman filter recursion applied on the linearised equivalent of the protein synthesis model together with an inverse transformation based on differential flatness theory that enables to retrieve estimates for the state variables of the initial non‐linear model. The proposed non‐linear feedback control and perturbations compensation method for the p 53–mdm 2 system can result in more efficient chemotherapy schemes where the infusion of medication will be better administered.Inspec keywords: proteins, molecular biophysics, biochemistry, Kalman filters, inverse problems, perturbation theoryOther keywords: nonlinear feedback control, p53 protein‐mdm2 inhibitor system, derivative‐free nonlinear Kalman filter, differential flatness theory, protein synthesis loop, diffeomorphism, protein synthesis model, feedback control law, nonmeasurable elements, modelling uncertainties, inverse transformation, nonlinear model, perturbation compensation method, chemotherapy schemes, medication infusion     

Biogenic synthesis of biopolymer‐based Ag–Au bimetallic nanoparticle constructs and their anti‐proliferative assessment

This study reports an eco‐friendly‐based method for the preparation of biopolymer Ag–Au nanoparticles (NPs) by using gum kondagogu (GK; Cochlospermum gossypium), as both reducing and protecting agent. The formation of GK‐(Ag–Au) NPs was confirmed by UV‐absorption, fourier transformed infrared (FTIR), atomic force microscopy (AFM), scanning electron microscope (SEM) and transmission electron microscope (TEM). The GK‐(Ag–Au) NPs were of 1–12 nm in size. The anti‐proliferative activity of nanoparticle constructs was assessed by MTT assay, confocal microscopy, flow cytometry and quantitative real‐time polymerase chain reaction (PCR) techniques. Expression studies revealed up‐regulation of p53, caspase‐3, caspase‐9, peroxisome proliferator‐activated receptors (PPAR) PPARa and PPARb, genes and down‐regulation of Bcl‐2 and Bcl‐x(K) genes, in B16F10 cells treated with GK‐(Ag–Au) NPs confirming the anti‐proliferative properties of the nanoparticles.Inspec keywords: nanomedicine, transmission electron microscopy, genetics, cellular biophysics, molecular biophysics, enzymes, nanofabrication, gold, silver, scanning electron microscopy, nanoparticles, Fourier transform infrared spectra, atomic force microscopy, biomedical materialsOther keywords: size 1.0 nm to 12.0 nm, Ag‐Au, anti‐proliferative assessment, eco‐friendly‐based method, anti‐proliferative activity, anti‐proliferative properties, biopolymer‐based Ag–Au bimetallic nanoparticle, Cochlospermum gossypium, gum kondagogu, biopolymer preparation, biogenic synthesis, UV‐absorption, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, atomic force microscopy, MTT assay, confocal microscopy, flow cytometry, caspase‐3, caspase‐9, peroxisome proliferator‐activated receptors, Bcl‐2 gene, Bcl‐x(K) gene, B16F10 cells     

Novel nanoplex‐mediated plant transformation approach

Here, a rapid and easy transformation by electroporation technique for gene transfer in plants using cell penetrating amino nanocomplex (nanoplex) has been demonstrated in Nicotiana. Nanoplex was prepared using cell penetrating amino acids (CPAs) such as poly‐L‐lysine (PLL) and Argenine (Arg), in combination with the gold nanoparticles (AuNPs). PLLs‐modified nanoplex with zeta potential of 34.2 ± 1.22 mV charge showed 63.3% efficiency for gene transformation in plant cells as compared to 60% when modified with Arg and the zeta potential was found to be 30.0 ± 0.83 mV; whereas, the transformation efficiency without nanoplex was found to be 6.6%. The findings indicate that the zeta potential of positively charged nanocomplex (AuNPs/CPAs/DNA/CPAs) increases the transformation efficiency because of their ability to protect the DNA from electroporation wave and endogenous enzyme damage. Transformation was confirmed by GUS assay and amplification of npt gene. This technique may open up new possibilities of gene transfer in plants, which will enable to produce large number of transgenic plants.Inspec keywords: biochemistry, electrokinetic effects, DNA, biomedical materials, nanomedicine, nanoparticles, gold, cellular biophysics, enzymes, genetics, molecular biophysics, genomicsOther keywords: nanoplex‐mediated plant transformation approach, electroporation technique, gene transfer, cell penetrating amino nanocomplex, cell penetrating amino acids, poly‐L‐lysine, Arg, gold nanoparticles, PLLs‐modified nanoplex, zeta potential, gene transformation, plant cells, transformation efficiency, positively charged nanocomplex, electroporation wave, npt gene, transgenic plants, AuNPs‐CPAs‐DNA‐CPAs, voltage 32.980000000000004 mV to 35.42 mV, voltage 29.169999999999998 mV to 30.830000000000002 mV, Au     

Co‐condensation synthesis of well‐defined mesoporous silica nanoparticles: effect of surface chemical modification on plasmid DNA condensation and transfection

Chemically modified mesoporous silica nanoparticles (MSNs) are of interest due to their chemical and thermal stability with adjustable morphology and porosity; therefore, it was aimed to develop and compare the MCM‐41 MSNs functionalised with imidazole groups (MCM‐41‐Im) to unmodified (MCM‐41‐OH) and primary amine functionalised (MCM‐41‐NH₂) MSNs for experimental gene delivery. The results show efficient transfection of the complexes of the plasmid and either MCM‐41‐NH₂ or MCM‐41‐Im. Furthermore, following transfection of HeLa cells using MCM‐41‐Im, an enhanced GFP expression was achieved consistent with the noticeable DNase1 protection and endosomal escape properties of MCM‐41‐Im using carboxyfluorescein tracer.Inspec keywords: condensation, mesoporous materials, silicon compounds, nanoparticles, DNA, surface chemistry, porosity, gene therapy, cellular biophysics, biomedical materials, nanomedicine, nanofabrication, molecular biophysics, biochemistryOther keywords: co‐condensation synthesis, surface chemical modification, plasmid DNA condensation, plasmid DNA transfection, chemical modified mesoporous silica nanoparticles, chemical stability, thermal stability, adjustable morphology, porosity, MCM‐41 MSN functionalisation, imidazole groups, MCM‐41‐OH, primary amine functionalised MSN, gene delivery, HeLa cell transfection, GFP expression, DNase1 protection, endosomal escape properties, carboxyfluorescein tracer, SiO₂      

Formulation and characterisation of a self‐nanoemulsifying drug delivery system of amphotericin B for the treatment of leishmaniasis

This study was aimed to develop a self‐nanoemulsifying drug delivery system (SNEDDS) for amphotericin B (AmB) potential use in leishmaniasis through topical and oral routes. Two formulations, formulation A and formulation B (FA and FB) of AmB loaded SNEDDS were developed by mixing their excipients through vortex and sonication. The SNEDDS formulation FA and FB displayed a mean droplet size of 27.70 ± 0.5 and 30.17 ± 0.7 nm and zeta potential −11.4 ± 3.25 and −13.6 ± 2.75 mV, respectively. The mucus permeation study showed that formulation FA and FB diffused 1.45 and 1.37%, respectively in up to 8 mm of mucus. The cell permeation across Caco‐2 cells monolayer was 10 and 11%, respectively. Viability of Caco‐2 cells was 89% for FA and 86.9% for FB. The anti‐leishmanial activities of FA in terms of IC₅₀ were 0.017 µg/ml against promastigotes and 0.025 µg/ml against amastigotes, while IC₅₀ values of FB were 0.031 and 0.056 µg/ml, respectively. FA and FB killed macrophage harboured Leishmania parasites in a dose‐dependent manner and a concentration of 0.1 µg/ml killed 100% of the parasites. These formulations have the potential to provide a promising tool for AmB use through oral and topical routes in leishmaniasis therapy.Inspec keywords: nanomedicine, drops, microorganisms, electrokinetic effects, cellular biophysics, drug delivery systems, monolayers, drugs, diseasesOther keywords: self‐nanoemulsifying drug delivery system, topical routes, oral routes, SNEDDS formulation, mucus permeation study, cell permeation, leishmaniasis treatment, amphotericin B, zeta potential, Caco‐2 cell monolayer, vortex, sonication, droplet size, Caco‐2 cell viability, antileishmanial activity, promastigotes, amastigotes, Leishmania parasites     

In vitro biological evaluation of anti‐diabetic activity of organic–inorganic hybrid gold nanoparticles

Diabetes mellitus has been considered as a heterogeneous metabolic disorder characterised by complete or relative impairment in the production of insulin by pancreatic β‐cells or insulin resistance. In the present study, propanoic acid, an active biocomponent isolated from Cassia auriculata is employed for the synthesis of propanoic acid functionalised gold nanoparticles (Pa@AuNPs) and its anti‐diabetic activity has been demonstrated in vitro. In vitro cytotoxicity of synthesised Pa@AuNPs was performed in L6 myotubes. The mode of action of Pa@AuNPs exhibiting anti‐diabetic potential was validated by glucose uptake assay in the presence of Genistein (insulin receptor tyrosine kinase inhibitor) and Wortmannin (Phosphatidyl inositide kinase inhibitor). Pa@AuNPs exhibited significant glucose uptake in L6 myotubes with maximum uptake at 50 ng/ml. Assays were performed to study the potential of Pa@AuNPs in the inhibition of protein‐tyrosine phosphatase 1B, α‐glucosidases, and α‐amylase activity.Inspec keywords: molecular biophysics, biomedical materials, sugar, enzymes, nanofabrication, gold, patient treatment, organic‐inorganic hybrid materials, biochemistry, diseases, cellular biophysics, nanoparticles, toxicology, nanomedicineOther keywords: glucose uptake assay, α‐amylase activity, organic–inorganic hybrid gold nanoparticles, diabetes mellitus, heterogeneous metabolic disorder, pancreatic β‐cells, insulin resistance, propanoic acid, antidiabetic potential, antidiabetic activity, in vitro cytotoxicity, L6 myotubes, Genistein, IRTK inhibitor, Wortmannin, P13K inhibitor, protein‐tyrosine phosphatase 1B, α‐glucosidases, Cassia auriculata, Au     

In vivo study of anti‐epidermal growth factor receptor antibody‐based iron oxide nanoparticles (anti‐EGFR‐SPIONs) as a novel MR imaging contrast agent for lung cancer (LLC1) cells detection

Superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with anti‐epidermal growth factor receptor monoclonal antibody (anti‐EGFR‐SPIONs) were characterised, and its cytotoxicity effects, ex vivo and in vivo studies on Lewis lung carcinoma (LLC1) cells in C57BL/6 mice were investigated. The broadband at 679.96 cm⁻¹ relates to Fe–O, which verified the formation of the anti‐EGFR‐Mab with SPIONs was obtained by the FTIR. The TEM images showed spherical shape 20 and 80 nm‐sized for nanoparticles and the anti‐EGFR‐SPIONs, respectively. Results of cell viability at 24 h after incubation with different concentrations of nanoprobe showed it has only a 20% reduction in cell viabilities. The synthesised nanoprobe administered by systemic injection into C57BL/6 mice showed good Fe tumour uptake and satisfied image signal intensity under ex vivo and in vivo conditions. A higher concentration of nanoprobe was achieved compared to non‐specific and control, indicating selective delivery of nanoprobe to the tumour. It is concluded that the anti‐EGFR‐SPIONs was found to be as an MR imaging contrast nanoagent for lung cancer (LLC1) cells detection.Inspec keywords: toxicology, biomedical MRI, lung, magnetic particles, biomedical materials, nanofabrication, nanomagnetics, transmission electron microscopy, nanomedicine, superparamagnetism, nanoparticles, iron compounds, proteins, cellular biophysics, molecular biophysics, cancer, tumours, Fourier transform infrared spectraOther keywords: MR imaging contrast agent, LLC1, superparamagnetic iron oxide nanoparticles, Lewis lung carcinoma cells, ex vivo conditions, cell viability, antiepidermal growth factor receptor antibody‐based iron oxide nanoparticles, antiEGFR‐SPION, lung cancer cell detection, antiepidermal growth factor receptor monoclonal antibody, cytotoxicity effects, C57BL‐6 mice, antiEGFR‐Mab, FTIR spectra, TEM, spherical shape, incubation, nanoprobe concentrations, systemic injection, Fe tumour uptake, image signal intensity, in vivo conditions, time 24.0 hour, Fe₃ O₄      

Characterisation of sol–gel method synthesised MgZnFe2 O4 nanoparticles and its cytotoxic effects on breast cancer cell line,MDA MB‐231 in vitro

In this study, nanocrystalline magnesium zinc ferrite nanoparticles were successfully prepared by a simple sol–gel method using copper nitrate and ferric nitrate as raw materials. The calcined samples were characterised by differential thermal analysis/thermogravimetric analysis, Fourier transform infrared spectroscopy and X‐ray diffraction. Transmission electron microscopy revealed that the average particle size of the calcined sample was in a range of 17–41 nm with an average of 29 nm and has spherical size. A cytotoxicity test was performed on human breast cancer cells (MDA MB‐231) and (MCF‐7) at various concentrations starting from (0 µg/ml) to (800 µg/ml). The sample possessed a mild toxic effect toward MDA MB‐231 and MCF‐7 after being examined with MTT (3‐[4, 5‐dimethylthiazol‐2‐yl]‐2, 5 diphenyltetrazolium bromide) assay for up to 72 h of incubation. Higher reduction of cells viability was observed as the concentration of sample was increased in MDA MB‐231 cell line than in MCF‐7. Therefore, further cytotoxicity tests were performed on MDA MB‐231 cell line.Inspec keywords: sol‐gel processing, nanoparticles, nanofabrication, magnesium compounds, zinc compounds, toxicology, biological organs, cancer, cellular biophysics, nanomedicine, calcination, differential thermal analysis, Fourier transform infrared spectra, X‐ray diffraction, transmission electron microscopy, particle size, organic compoundsOther keywords: sol‐gel method, cytotoxic effects, breast cancer cell line, MDA MB‐231 in vitro, nanocrystalline magnesium zinc ferrite nanoparticles, copper nitrate, ferric nitrate, raw materials, calcined samples, differential thermal analysis, thermogravimetric analysis, Fourier transform infrared spectroscopy, X‐ray diffraction, transmission electron microscopy, average particle size, cytotoxicity testing, human breast cancer cells, mild toxic effect, 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyltetrazolium bromide) assay, cell viability, MCF‐7, MDA MB‐231 cell line, size 17 nm to 41 nm     

Competitive numerical analysis for stochastic HIV/AIDS epidemic model in a two‐sex population

This study is an attempt to explain a reliable numerical analysis of a stochastic HIV/AIDS model in a two‐sex population considering counselling and antiretroviral therapy (ART). The authors are comparing the solutions of the stochastic and deterministic HIV/AIDS epidemic model. Here, an endeavour has been made to explain the stochastic HIV/AIDS epidemic model is comparatively more pragmatic in contrast with the deterministic HIV/AIDS epidemic model. The effect of threshold number H ^* holds on the stochastic HIV/AIDS epidemic model. If H ^*  < 1 then condition helps us to control disease in a two‐sex human population while H ^*  > 1 explains the persistence of disease in the two‐sex human population. Lamentably, numerical methods such as Euler–Maruyama, stochastic Euler, and stochastic Runge–Kutta do not work for large time step sizes. The recommended structure preserving framework of the stochastic non‐standard finite difference (SNSFD) scheme conserve all vital characteristics such as positivity, boundedness, and dynamical consistency defined by Mickens. The effectiveness of counselling and ART may control HIV/AIDS in a two‐sex population.Inspec keywords: diseases, stochastic processes, epidemics, patient treatment, finite difference methodsOther keywords: two‐sex human population, antiretroviral therapy, competitive numerical analysis, stochastic HIV‐AIDS epidemic model, structure preserving framework, stochastic nonstandard finite difference scheme, SNSFD scheme, deterministic HIV‐AIDS epidemic model     

Architecture‐dependent robustness in a class of multiple positive feedback loops

Many types of multiple positive feedbacks with each having potentials to generate bistability exist extensively in natural, raising the question of why a particular architecture is present in a cell. In this study, the authors investigate multiple positive feedback loops across three classes: one‐loop class, two‐loop class and three‐loop class, where each class is composed of double positive feedback loop (DPFL) or double negative feedback loop (DNFL) or both. Through large‐scale sampling and robustness analysis, the authors find that for a given class, the homogeneous DPFL circuit (i.e. the coupled circuit that is composed of only DPFLs) is more robust than all the other circuits in generating bistable behaviour. In addition, stochastic simulation shows that the low stable state is more robust than the high stable state in homogeneous DPFL whereas the high‐stable state is more robust than the low‐stable state in homogeneous DNFL circuits. It was argued that this investigation provides insight into the relationship between robustness and network architecture.Inspec keywords: cellular biophysics, feedback, sampling methods, stochastic processesOther keywords: network architecture, low stable state, stochastic simulation, bistable behaviour, homogeneous DPFL circuit, robustness analysis, large‐scale sampling, DNFL, double negative feedback loop, double positive feedback loop, three‐loop class, two‐loop class, one‐loop class, cell architecture, bistability, multiple positive feedback loops, architecture‐dependent robustness