Probing binding mode between sodium acid pyrophosphate and albumin: multi-spectroscopic and molecular docking analysis.

Sodium acid pyrophosphate (SAPP) food additive is widely used as a preservative, bulking agent, chelating agent, emulsifier and pH regulator. It is also used as an improver of color and water retention capacity in the processing of various types of seafood, canned food, cooked meat and flour products. For the first time, we evaluated the SAPP interaction with bovine serum albumin (BSA) using spectroscopic methods including UV-Vis absorption, fluorescence spectroscopy, and surface plasmon resonance, and docking analysis to understand the mechanisms of complex formation and binding. The fluorescence intensity of BSA reduces when titrated with various concentrations of SAPP by forming a complex with BSA via a static quenching mechanism. The binding constant between BSA and SAPP decreased from 123,300 to 15,800 (M-1) with rising temperature, which indicates a decrement in complex formation owing to the interaction of SAPP with BSA. A negative ΔG° value means that SAPP binds spontaneously to BSA at all temperatures, and both ΔH° and ΔS° negative values indicate that hydrogen bonds (H-bonding) and van der Waals forces are the primary forces involved in the binding processes. The UV-Vis spectrum of BSA reduced upon increasing SAPP concentrations due to forming a new ground state complex between SAPP and BSA. Molecular docking study shows that residues Arg256, Ser259, Ser286, Ile 289 and Ala 290 play an important role in SAPP binding process to site I (subdomain IIA) of BSA through H-bonding and van der Waals forces, which is supported by the thermodynamic study.Communicated by Ramaswamy H. Sarma.

Spectroscopic aspects on the interaction of nisin with serum albumin: thermodynamic and kinetic studies.

Introduction: Nisin is a bacteriocin produced by Streptococcus and Lactococcus species and has antimicrobial activity against other bacteria. Nisin omits the need to use chemical preservatives in food due to its biological preserving properties. Methods: In the present in vitro study, we investigated nisin interaction with bovine serum albumin (BSA) using fluorescence spectroscopy and surface plasmon resonance (SPR) analysis to obtain information about the mechanisms of BSA complex formation with nisin. Results: The BSA fluorescence intensity values gradually diminished with rising nisin concentration. The BSA fluorescence quenching analysis indicated that a combined quenching mechanism plays the main role. Finally, the Kb values were reduced with increasing temperature, which is demonstrative of nisin-BSA complex stability decrease at high temperatures. The negative values of ΔH° and ΔS° showed that hydrogen bonds and van der Waals forces are the foremost binding force between BSA and nisin. Meanwhile, the negative values of ΔG° demonstrated the exothermic and random nature of the reaction process. The results of the SPR verified the gained results through the fluorescence spectroscopy investigation, which denoted that the BSA affinity to nisin diminished upon increasing temperature. Conclusion: Overall, fluorescence spectroscopy and SPR results showed that the BSA interaction with nisin decreased with rising temperatures.

Pharmacokinetic and toxicological overview of propyl gallate food additive.

The progressive use of food additives in "ultra-processed" food has increased attention to them. Propyl gallate (PG) is an essential synthetic preservative that commonly used in food, cosmetics, and pharmacies as an antioxidant. This study aimed to outline the existing evidence on the toxicological studies of PG including its physicochemical properties, metabolism, and pharmacokinetics effects. The methods include updated searches for the relevant databases. The EFSA has evaluated the use of PG in food industry. It establishes an acceptable daily intake (ADI) of 0.5 mg/kg bw per day. Based on exposure assessment, it can be concluded that at the current level of use, PG is not of safety concern.

Synergizing Functional Nanomaterials with Aptamers Based on Electrochemical Strategies for Pesticide Detection: Current Status and Perspectives.

Owing to the high toxicity and large-scale use of pesticides, it is imperative to develop selective, sensitive, portable, and convenient sensors for rapid monitoring of pesticide. Therefore, the electrochemical detection platform offers a promising analytical approach since it is easy to operate, economical, efficient, and user-friendly. Meanwhile, with advances in functional nanomaterials and aptamer selection technologies, numerous sensitivity-enhancement techniques alongside a widespread range of smart nanomaterials have been merged to construct novel aptamer probes to use in the biosensing field. Hence, this study intends to highlight recent development and promising applications on the functional nanomaterials with aptamers for pesticides detection based on electrochemical strategies. We also reviewed the current novel aptamer-functionalized microdevices for the portability of pesticides sensors. Furthermore, the major challenges and future prospects in this field are also discussed to provide ideas for further research.

Applications of scaffold-based advanced materials in biomedical sensing.

There have been many efforts to synthesize advanced materials that are capable of real-time specific recognition of a molecular target, and allow the quantification of a variety of biomolecules. Scaffold materials have a porous structure, with a high surface area and their intrinsic nanocavities can accommodate cells and macromolecules. The three-dimensional structure (3D) of scaffolds serves not only as a fibrous structure for cell adhesion and growth in tissue engineering, but can also provide the controlled release of drugs and other molecules for biomedical applications. There has been a limited number of reports on the use of scaffold materials in biomedical sensing applications. This review highlights the potential of scaffold materials in the improvement of sensing platforms and summarizes the progress in the application of novel scaffold-based materials as sensor, and discusses their advantages and limitations. Furthermore, the influence of the scaffold materials on the monitoring of infectious diseases such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and bacterial infections, was reviewed.

Silencing of HMGA2 by siRNA Loaded Methotrexate Functionalized Polyamidoamine Dendrimer for Human Breast Cancer Cell Therapy.

The transcription factor high mobility group protein A2 (HMGA2) plays an important role in the pathogenesis of some cancers including breast cancer. Polyamidoamine dendrimer generation 4 is a kind of highly branched polymeric nanoparticle with surface charge and highest density peripheral groups that allow ligands or therapeutic agents to attach it, thereby facilitating target delivery. Here, methotrexate (MTX)- modified polyamidoamine dendrimer generation 4 (G4) (G4/MTX) was generated to deliver specific small interface RNA (siRNA) for suppressing HMGA2 expression and the consequent effects on folate receptor (FR) expressing human breast cancer cell lines (MCF-7, MDA-MB-231). We observed that HMGA2 siRNA was electrostatically adsorbed on the surface of the G4/MTX nanocarrier for constructing a G4/MTX-siRNA nano-complex which was verified by changing the final particle size and zeta potential. The release of MTX and siRNA from synthesized nanocomplexes was found in a time- and pH-dependent manner. We know that MTX targets FR. Interestingly, G4/MTX-siRNA demonstrates significant cellular internalization and gene silencing efficacy when compared to the control. Besides, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay demonstrated selective cell cytotoxicity depending on the folate receptor expressing in a dose-dependent manner. The gene silencing and protein downregulation of HMGA2 by G4/MTX-siRNA was observed and could significantly induce cell apoptosis in MCF-7 and MDA-MB-231 cancer cells compared to the control group. Based on the findings, we suggest that the newly developed G4/MTX-siRNA nano-complex may be a promising strategy to increase apoptosis induction through HMGA2 suppression as a therapeutic target in human breast cancer.

Lysine Decorated Solid Lipid Nanoparticles of Epirubicin for Cancer Targeting and Therapy.

Purpose: Cancer is an example of the most important growing diseases in human society and scientists are trying to treat it without considerable side effects on patient's health. Solid lipids are colloidal nanoparticles that were used in drug delivery due to their several advantages. Methods: In this work, surface modified targeted solid lipid nanoparticles (SLNs) were fabricated by nano-homogenizer using tripalmitin glyceride and stearic acid as lipid constituents. The size of nanoparticles and morphological evaluations were surveyed using particle size analyzer, scanning electron microscopy; Fourier transforms infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Results: The particle size of 148.5 and appropriate polydispersity index were achieved for lipid nanoparticles with an entrapment efficiency of 86.1%. The FT-IR analysis confirmed the coupling of lysine to the free functional group of SLNs. DSC proved the conjugation of amino acid to the surface of carriers. The in vitro epirubicin (EPI) release test exhibited the further controlled release phenomenon for the lysine conjugated nanoparticles. The cytotoxicity assay showed lower IC50 of lysine conjugated SLNs of EPI on the investigated cell line. Conclusion: These studies showed that the fabricated targeted carrier has a very remarkable anticancer effect on breast cancer cell lines in comparison with pure drug.

Kinetic and thermodynamic insights into interaction of erlotinib with epidermal growth factor receptor: Surface plasmon resonance and molecular docking approaches.

Epidermal growth factor receptor (EGFR) plays an important role in cell proliferation at non-small cell lung cancer (NSCLC). Therefore, targeted therapy of cancer via this kind of receptor is highly interested. Small molecule drugs such as erlotinib and gefitinib inhibit EGFR tyrosine kinase and thus suppress cell proliferation. At this paper, erlotinib interaction with EGFR on the cell surface was studied via surface plasmon resonance (SPR) and molecular docking methods. Kinetic parameters indicated that erlotinib affinity toward EGFR was increased through increment of temperature. The thermodynamic analysis showed that van der Waals and hydrogen binding forces play a major role in the interaction of erlotinib with EGFR. Docking results showed that Domain II in EGFR has role in the interaction with erlotinib. Besides, the binding energy for this interaction was -10.7 kcal/mol, which is suitable for binding of erlotinib to Domain II in EGFR.

Nano-based delivery systems for berberine: A modern anti-cancer herbal medicine.

Berberine (BBR) is an isoquinoline alkaloid belonging to the structural class of protoberberines. BBR has been used in traditional medicine to treat diseases, such as type 2 diabetes and hypercholesterolemia. BBR inhibits cancer cell growth and induces apoptosis. However, BBR has significant drawbacks as a chemotherapeutic agent, including poor solubility, and induction of drug resistance, limiting its application in chemotherapy. Hence, combination therapy could not only deal with the problems related to single-agent chemotherapy but could also improve the therapeutic index of anticancer drugs. Co-administration of drugs may show pharmaceutical incompatibility due to conflicting physicochemical features. BBR can be used in nanoparticle-based single drug delivery, and in co-delivery systems designed to accommodate drugs and deliver them simultaneously into cancer cells. In this review, we will summarize the use of BBR, including BBR as a single chemotherapeutic agent and the combination of BBR with traditional anti-cancer drugs or herbal medicines in nanoparticle-based delivery systems.

Apoptosis and DNA damage induced by silica nanoparticles and formaldehyde in human lung epithelial cells.

Human exposure to silica nanoparticles (SNPs) and formaldehyde (FA) is increasing and this has raised some concerns over their possible toxic effects on the exposed working populations. Notwithstanding several studies in this area, the combined toxicological effects of these contaminants have not been yet studied. Therefore, this in vitro study was designed to evaluate the SNPs and FA combined toxicity on human lung epithelial cells (A549 cells). The cells were exposed to SNPs and FA separately and in combined form and the single and combined toxicity of SNPs and FA were evaluated by focusing on cellular viability, DNA damage, and apoptosis via MTT, DAPI staining, DNA ladder, and Annexin V-FITC apoptosis assays. The results showed a significant increase in cytotoxicity, DNA damage, and chromatin fragmentation and late apoptotic\necrotic rates in combined treated cells compared with SNPs and FA-treated cells (P value < 0.05). Two-factorial analysis showed an additive toxic interaction between SNPs and FA. Eventually, this can be deduced that workers exposed simultaneously to SNPs and FA may be at high risk compared with exposure to each other.

Co-delivery of curcumin and Bcl-2 siRNA by PAMAM dendrimers for enhancement of the therapeutic efficacy in HeLa cancer cells.

Co-delivery of therapeutic agents and small interfering RNA (siRNA) can be achieved by a suitable nanovehicle. In this work, the solubility and bioavailability of curcumin (Cur) were enhanced by entrapment in a polyamidoamine (PAMAM) dendrimer, and a polyplex was formed by grafting Bcl-2 siRNA onto the surface amine groups to produce PAMAM-Cur/Bcl-2 siRNA nanoparticles (NPs). The synthesized polyplex NPs had a particle size of ∼180 nm, and high Cur loading content of ∼82 wt%. Moreover, the PAMAM-Cur/Bcl-2 siRNA NPs showed more effective cellular uptake, and higher inhibition of tumor cell proliferation compared to PAMAM-Cur nanoformulation and free Cur, due to the combined effect of co-delivery of Cur and Bcl-2 siRNA. The newly described PAMAM-Cur/Bcl-2 siRNA polyplex NPs could be a promising co-delivery nanovehicle.

Nanomaterials and new biorecognition molecules based surface plasmon resonance biosensors for mycotoxin detection.

Mycotoxins are highly toxic secondary metabolites, which may contaminate many types of food and feeds. These toxins have serious health risks for both human and animals. One of the effective ways to prevent food contamination and protect people against mycotoxins is based on timely detection. Several methods like enzyme-linked immunosorbent assay and affinity chromatography are commercially available for this purpose. Nevertheless, sensitive, fast, simple, low-cost, and portable devices are absolutely required for a fast point-of care information and making decisions. Application of biosensors appears to be a possible technique to meet this need for mycotoxins analyze. The present study has been focused on the literature update of smart using of biosensing for detection of mycotoxin at both academic and industrial levels in order to replace conventional chromatographic methods. Surface plasmon resonance (SPR) as one of the relatively novel and simple analytical method has been proven for rapid, sensitive, label-free detection and widely used for qualitative and quantitative analysis of multiplexed pollutant in real-time. This paper aims to provide an extensive overview on biosensors for mycotoxin detection by highlighting the main biorecognition elements. Moreover, SPR principles, assay formats, and signal enhancement are summarized.

Molecular and technical aspects on the interaction of serum albumin with multifunctional food preservatives.

Synthetic food preservatives like sodium acetate (SA), sodium benzoate (SB), potassium sorbate (PS) and Butyl paraben (BP) have been widely used in food and pharmacy industries. One of the toxicological aspects of food additives is evaluation of their interaction with serum proteins such as albumin. These additives interaction with human serum albumin (HSA) can exert considerable effect on the absorption, distribution, metabolism and toxicity of chemical compounds. It should be noticed that the aforementioned food preservatives intake increase mainly in the presence of glucose may lead to complex formation of SA, SB, PS and BP with HSA and accelerate the development of variety disease such as cancer, diabetes, multiple sclerosis, brain damage, nausea and cardiac disease. Therefore, to understand the mechanisms of aforementioned food additives interaction and conformational changes of proteins, we aim to review various studies that investigated albumin interaction with these additives using several procedures.

Nigella sativaand its Derivatives as Food Toxicity Protectant Agents.

Exposure to food toxins generate multiple adverse health effects. Heavy metals, antibiotics residue, mycotoxins, pesticides and some food additives are examples of the most important food toxins. The common mechanism of toxicity and carcinogenicity effects of food toxins is the generation of oxidative stress that leads to DNA damages. Moreover, based on epidemiologic evidence unhealthy eating habits and food toxicities are associated with cancers occurrence. Therefore, application of bioactive food additives as harmless or safe components in food industry is expensive. Nigella sativa L. is a broadly used herb-drug for various diseases all over the world and has been used as preservative and food additive. Based on various studies N. sativa has shown various pharmacological activities including therapeutic efficacy against different human diseases and antioxidant anti-inflammatory effects against environmental toxins. N. sativa decreases the adverse health effects induced by mentioned food toxins via modulating the action of antioxidant enzymes such as glutathione peroxidase (GPx), glutathione-S-transferase catalase and act as reactive oxygen species (ROS) scavengers in different organs. Besides, N. sativa and thymoquinone (TQ) have protective effects on food products through removal and inhibition of various toxic compounds. Therefore, in the present review we will describe all protective effects of N. sativa and its main constituents, TQ, against food induced toxicities.

Ethambutol-Loaded Solid Lipid Nanoparticles as Dry Powder Inhalable Formulation for Tuberculosis Therapy.

Ethambutol hydrocloride (EMB) is an anti-tuberculosis drug, which is commonly used as a protection agent against of unrecognized resistance to other drugs employed to treat this disease. Since oral form of EMB has some side effects and cellular toxicity, direct administration of EMB into lungs seems to be an attractive and reasonable option in order to overcome these side effects. Our main goal in this study was assessment of pulmonary administration through dry powder inhaler (DPI) using EMB-loaded solid lipid nanoparticles (SLNs). We prepared EMB-loaded SLNs using two techniques (hot homogenization and ultrasonication). DPI formulations were made by spray drying of EMB-loaded SLNs with and without mannitol. For investigation of flowbility of the prepared powders, Carr's index and Hausner ratio, and for in vitro deposition of the powders, Next Generation Impactor (NGI) analysis were used. The encapsulation efficiency and particle size of obtained particles were higher than 98% and sub-100 nm, respectively. Toxicity investigation of EMB-loaded SLNs via MTT assay showed biocompatibility and non-toxicity of the SLNs. Results of flowability and aerodynamic traits assessment of EMB-loaded SLN DPI powder confirmed the suitability of prepared powders. Overall, the attained results showed that EMB-loaded SLN DPI has high potential for direct treatment of tuberculosis.

The protective effect of thymoquinone on tert-butylhydroquinone induced cytotoxicity in human umbilical vein endothelial cells.

2-tert-Butyl-4-hydroquinone (TBHQ) is used for inhibition of oxidative rancidity in the food industry. However, this antioxidant can stimulate cytotoxicity in human umbilical vein endothelial cells (HUVECs). Thus, potential protective effects of thymoquinone (TQ) against TBHQ-induced cytotoxicity were investigated. Cytotoxicity was evaluated via MTT, flow cytometry, DAPI staining and DNA fragmentation methods. The obtained results revealed that treatment of HUVECs with TQ enhanced the cell viability rate and it had potential to reduce the cytotoxicity effect of TBHQ in cells. Also, in a combined regime of TQ and TBHQ, apoptosis was reduced compared to the cells treated with TBHQ (p < 0.05). Similarly, TQ had a protective effect on DNA and chromatin fragmentation of the cells treated with TBHQ. Finally, it can be concluded that TQ could be used as a protective agent against cytotoxicity induced by TBHQ in HUVECs.

Nanomaterials based surface plasmon resonance signal enhancement for detection of environmental pollutions.

Due to the nearby relationship between human health, socioeconomic development and environmental pollution, the detection and identification of environmental pollutants need more attention. Therefore, the development of suitable analytical devices that are sensitive, specific, precise, quick, and easy-to-use are required to resolve the increased request for legislative action on environmental pollution control and early detection of rising pollutants. Currently, the development of biosensing instruments attracted important attention because of their high selectivity, sensitivity, simplicity, reliability, low-cost and real-time response. Surface plasmon resonance (SPR) sensor as an example of portable, rapid, and smart biosensing devices widely used for qualitative and quantitative detection of multiplexed pollutant in real-time. Thus, SPR principles, assay formats, surface modification methods and signal enhancement are summarized in this review. Moreover, applications of SPR in the detection of pesticide, polycyclic aromatic hydrocarbons (PAHs), heavy metals and polychlorinated biphenyls (PCBs) over the past decade is discussed.

Cytotoxicity and Genotoxicity Assessment of Ascorbyl Palmitate (AP) Food Additive.

Purpose: Ascorbyl palmitate (AP) is a widely used food additive in food industry. In this study, AP was evaluated for potential cyto-genotoxicity on Human Umbilical Vein Endothelial Cells (HUVECs). Methods: MTT assay and flow cytometry analysis was used for cytotoxicity evaluation, while genotoxicity was carried out using DAPI staining assays and real time PCR. Results: The growth of HUVECs was decreased upon treatment with AP in dose-and time-dependent manner. Early/late apoptosis percentage in HUVECs treated with this additive was detected using flow cytometry analysis. Also morphology of DAPI stained HUVECs clearly showed chromatin fragmentation. Furthermore, real time PCR results showed that AP induces apoptosis by up-regulation of caspase-3, 9 and down-regulation of Bcl-2 ratio. Conclusion: The present results indicated that AP has capability to induce apoptosis in HUVECs and its better to make a thorough analysis about its extensive application in food industry.

Surface functionalized dendrimers as controlled-release delivery nanosystems for tumor targeting.

Dendrimers are nano-sized and three-dimensional macromolecules with well-defined globular architecture and are widely used in various aspects such as drug and gene delivery owing to multivalent and host-guest entrapment properties. However, dendrimers like other nanomaterials have some disadvantages for example rapid clearance by reticuloendothelial system, toxicity due to interaction of amine terminated group with cell membrane, low transfection efficiency and lack of controlled release behavior, which reduce their therapeutic efficiency. To solve these problems, surface functionalization of dendrimers can be carried out. Surface functionalization not only mitigates this obstacle but also renders excessive specificity to dendrimer to improve efficiency of cancer therapy. Specific properties in cancer cell compared to normal cells such as overexpression of various receptors and difference in biological condition like pH, temperature and redox of tumor environment can be an appropriate strategy to increase site-specific targeting efficiency. Therefore, in this article we focus on numerous functionalization strategies, which are used in the modification of dendrimers through attachment of lipid, amino acid, protein/peptide, aptamer, vitamin, antibody. Moreover, increased biocompatibility, site-specific delivery based on various ligands, enhanced transfection efficiency, sustained and controlled release behavior based on stimuli responsiveness are benefits of functionalized dendrimer which we discuss in this review. Overall, these functionalized dendrimers can open a new horizon in the field of targeted drug and gene delivery.

Nanomaterials and phase sensitive based signal enhancment in surface plasmon resonance.

Measurement of small molecules in extremely dilute concentrations of analyte play an important role in different issues ranging from food industry to biological, pharmaceutical and therapeutical applications. Surface plasmon resonance (SPR) sensors can be a suitable choice for detection of small molecules based on interactions with biomolecules. However, sensitivity of the system for detection of these molecules is very low. Improving sensitivity has been a challenge for years. Therefore, different methods have been used to enhance SPR signals. The SPR signal enhancement using numerous nanomaterials has provided exciting results. Among various nanomaterials, metal nanoparticles (for instance gold, silver and magnetic nanoparticles), quantum dots, nanorads, and carbon-based nanostructures have got much attention due to ease in fabrication, appropriate size and shape. In addition to the advantages provided by using nanomaterials, signal enhancement provided by the appropriate use of phase information of the reflected light could be also important to improve SPR sensitivity. Phase-sensitive SPR sensors are able to detect infinitesimal changes in external properties of target while traditional type of SPR cannot demonstrate these changes. This article provides an overview on signal enhancment in SPR using nanomaterials and properties of light. We also discuss on recent progresses of the field, describing basic concepts concerning nanostructures as well as phase-sensitive sensors as platform for enhancement of signal in SPR.