Health concerns of various nanoparticles: A review of their in vitro and in vivo toxicity

Nanoparticles (NPs) are currently used in diagnosis and treatment of many human diseases, including autoimmune diseases and cancer. However, cytotoxic effects of NPs on normal cells and living organs is a severe limiting factor that hinders their use in clinic. In addition, diversity of NPs and their physico-chemical properties, including particle size, shape, surface area, dispersity and protein corona effects are considered as key factors that have a crucial impact on their safe or toxicological behaviors. Current studies on toxic effects of NPs are aimed to identify the targets and mechanisms of their side effects, with a focus on elucidating the patterns of NP transport, accumulation, degradation, and elimination, in both in vitro and in vitro models. NPs can enter the body through inhalation, skin and digestive routes. Consequently, there is a need for reliable information about effects of NPs on various organs in order to reveal their efficacy and impact on health. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges. © 2018 by the authors. Licensee MDPI, Basel, Switzerland

Effects of pirfenidone, vitamin E, and pirfenidone�vitamin E combination in paraquat-induced pulmonary fibrosis

Paraquat-induced pulmonary fibrosis is a progressive and fatal interstitial lung disease, a condition for that, there is no effective treatment and its prognosis is appalling. Since multiple coactivated pathways are involved, targeting these pathways using combination regimens is plausible for successful therapy. So, the aim of the present study was to evaluate the therapeutic efficacy of pirfenidone�vitamin E combination therapy in (paraquat) PQ-induced lung fibrosis model. After the development of PQ-induced lung fibrosis, pirfenidone, vitamin E, pirfenidone plus vitamin E, and water (as a vehicle) were orally administered for 14 consecutive days (From day 14 to day 28). The comparison of efficacies was performed by evaluating histopathology changes, hydroxyproline content, and oxidative stress. Either pirfenidone or vitamin E solely could recover the pathological changes of paraquat, decreased lipid peroxidation, and restored the antioxidant enzymes towards normal values. Hydroxyproline content was significantly reduced by both pirfenidone and vitamin E administration. Concurrent treatment with pirfenidone and vitamin E intensified all of these therapeutics effects indicating more potent antifibrotic and anti-inflammatory impacts. Therefore, pirfenidone plus vitamin E offers potential as a combination therapy for the treatment of paraquat-induced pulmonary fibrosis. © 2020, Springer-Verlag London Ltd., part of Springer Nature

Nigella sativa L., supplementary plant with anticholinesterase effect for cognition problems: A kinetic study

Background: The average lifespan and the aging population are rising worldwide. So Neurodegenerative Disease (ND) will be one of the most common challenges associated with this population and would be more prevalent in future. The use of Acetylcholinesterase (AChE) inhibitors is one of the most important strategies for memory impairment. Medicinal plants are the most known natural source for accessing the new therapeutic agents. Objective: In this work, we aimed to study in vitro anticholinesterase effect of different concentrations (10, 100, 250, 500, 750 and 1000 �g/ml) of total extract of N. sativa (NTE) and its separated fractions and to study the kinetic of AChE enzyme in the presence of two concentrations of NTE (10 and 100 �g/ml). Methods: Maceration method was used for NTE preparation and different fractions of Petroleum Ether (PTE), Chloroform (CHF) and Methanol (MF). NTE, fractions and the main component of the plant, Thymoquinone (TQ), were assayed for AChE inhibition, using Ellman�s method. Kinetic study of the AChE enzyme was studied in the presence of NTE at 10 and 100 �g/ml using Linweaver- Burk plot too. Results: NTE and all the separated fractions inhibited AChE enzyme in a concentration-dependent manner. The greatest inhibition was shown by CHF and PEF fractions (86.97 and 79.99 at 1000 �g/ml, respectively). With less intensity, NTE, TQ and MF exhibited 76.32, 68.98 and 48.39 enzyme inhibition at 1000�g/ml, respectively. The least IC50 value was due to CHF fraction in AChE inhibition (98.28 ± 6.74 �g/ml). Kinetic profile exhibited the mixed mode of AChE inhibition by NTE. This indicates that a particular substance could not be responsible for AChE inhibition, and probably a collection of phytochemicals are involved in this process. Conclusions: N. sativa is a good candidate for seeking the new anticholinesterase agent and could be considered as a good supplement for the health of the elderly. © 2020 Bentham Science Publishers

ZEB1 and ZEB2 gene editing mediated by CRISPR/Cas9 in A549 cell line

OBJECTIVES: One of the best approaches for recognition of protein function is the induction of mutations for a gene knockout. In line with this strategy, gene editing tools allow researchers to induce these mutations. Lung cancer is one of the leading causes of death worldwide. ZEB1 and ZEB2 genes are the candidates for this disease. METHODS: The ZEB1 and ZEB2 knockout in the non-small cell lung cancer cell line (A549 cell) was investigated. Purification of recombination plasmids was performed from bacteria and then was transported to the A549 cell line. The deletion of ZEB1 and ZEB2 were examined by PCR. RESULTS: The results demonstrated the mutation and deletion in ZEB1 and ZEB2 genes. Based on the findings of this study, A549 cells were transfected with the vectors carrying the sgRNA/Cas9, simultaneously. The DNA fragment demonstrated the presence of indels in target sites as well as provided the potential of CRISPR/Cas9 system. CONCLUSION: CRISPR/Cas9 offers a great potential as an efficient technique for editing of ZEB1 and ZEB2 genes in A549 cell line (Tab. 1, Fig. 6, Ref. 44). Text in PDF www.elis.sk. © 2020, Comenius University

The effects of functionalization of carbon nanotubes on toxicological parameters in mice

Carbon nanotubes (CNTs) have emerged as a new class of multifunctional nanoparticles in biomedicine, but their multiple in vivo effects remain unclear. Also, the impact of various functionalization types and duration of exposures are still unidentified. Herein, we report a complete toxicological study to evaluate the effects of single- and multiwalled carbon nanotubes (SWCNTs and MWCNTs) with either amine or carboxylic acid (COOH) surface functional groups. The results showed that significant oxidative stress and the subsequent cell apoptosis could be resulted in both acute and, mainly, in chronic intravenous administrations. Also, male reproductive parameters were altered during these exposures. The amino-functionalized CNTs had more toxic properties compared with the COOH functionalized group, and also, in some groups, the multiwalled nanotubes were more active in eliciting cytotoxicity than the single-walled nanotubes. Interestingly, the SWCNTs-COOH had the least alterations in most of the parameters. Evidently, it is concluded that the toxicity of CNTs in specific organs can be minimized through particular surface functionalizations. © The Author(s) 2020