Natural and Synthetic Peptides to Control Drug-resistant Pathogens.

Due to the excessive and inappropriate use of antibiotics in farming and clinic, pathogens developed resistance mechanisms to currently used drugs. Thus, because of this resistance, drugs become ineffective, leading to public health problems worldwide. According to the World Health Organization (WHO), microbial resistance to drugs is one of the most threats that humanity must face. Therefore, it is imperative to seek alternative methods to overcome microbial resistance. Here, the potential of natural or synthetic antimicrobial peptides to overcome microbial resistance will be discussed, and how peptides could be a source for new therapeutics molecules. In this context, antimicrobial peptides (natural or synthetic) are considered promising molecules based on their antifungal, antiviral, and antibacterial properties, making them eligible for developing new drugs. In addition, they can act synergistically with existing drugs on the market, revealing a broad spectrum of applications.

Cytocompatibility and osteogenic differentiation of stem cells from human exfoliated deciduous teeth with cotton cellulose nanofibers for tissue engineering and regenerative medicine.

Cellulose nanofibers (CNFs) are natural polymers with physical-chemical properties that make them very attractive for modulating stem cell differentiation, a crucial step in tissue engineering and regenerative medicine. Although cellulose is cytocompatible, when materials are in nanoscale, they become more reactive, needing to evaluate its potential toxic effect to ensure safe application. This study aimed to investigate the cytocompatibility of cotton CNF and its differentiation capacity induction on stem cells from human exfoliated deciduous teeth. First, the cotton CNF was characterized. Then, the cytocompatibility and the osteogenic differentiation induced by cotton CNF were examined. The results revealed that cotton CNFs have about 6-18 nm diameters, and the zeta potential was -10 mV. Despite gene expression alteration, the cotton CNF shows good cytocompatibility. The cotton CNF induced an increase in phosphatase alkaline activity and extracellular matrix mineralization. The results indicate that cotton CNF has good cytocompatibility and can promote cell differentiation without using chemical inducers, showing great potential as a new differentiation inductor for tissue engineering and regenerative medicine applications.

The distinct effect of titanium dioxide nanoparticles in primary and immortalized cell lines.

The titanium dioxide nanoparticles (NPs) have been applied to biomedical, pharmaceutical, and food additive fields. However, the effect on health and the environment are conflicting; thus, it has been reviewing several times. In this context, establishing standard robust protocols for detecting cytotoxicity and genotoxicity of nanomaterials became essential for nanotechnology development. The cell type and the intrinsic characteristics of titanium dioxide NPs can influence nanotoxicity. In this work, the cyto- and genotoxicity effects of standard reference material titanium dioxide NPs in primary bovine fibroblasts and immortalized Chinese hamster ovary epithelial (CHO) cells were determined and compared for the first time. Titanium dioxide NPs exposure revealed no cytotoxicity for primary bovine fibroblasts, while only higher concentrations tested (10 µg/ml) induce genotoxic effects in this cell model. In contrast, the lower concentrations of the titanium dioxide NPs cause the cyto- and genotoxic effects in CHO cells. Therefore, our finding indicates that the CHO line was more sensitive toward the effects of titanium dioxide NPs than the primary bovine fibroblast, which should be valuable for their environmental risk assessment.

Corrigendum to: The distinct effect of titanium dioxide nanoparticles in primary and immortalized cell lines.

[This corrects the article DOI: 10.1093/toxres/tfab040.].

Cotton cellulose nanofiber/chitosan nanocomposite: characterization and evaluation of cytocompatibility.

Cellulose is a renewable polymer quite abundant on the Earth and very attractive for applications in the construction of eco-friendly biomedical products. The aim of this study was to investigate the chemical-physical characteristics of cotton cellulose nanofiber (CCN)/chitosan nanocomposite and its cytocompatibility with human embryonic kidney cells. First, the chemical composition, swelling ratio and surface topography of the nanocomposite were evaluated. Cytocompatibility was then assessed through spreading, proliferation and viability of cells. The experimental results showed that the CCN was an effective nanomaterial agent for increasing the roughness surface of chitosan film. Cell proliferation and changes in cell morphology indicated that the nanocomposite led to improved cell spreading and growth. Cell viability did not decrease after 24 h. However, the cell survival on the nanocomposite was affected at 72 h. The results indicate that CCN/chitosan nanocomposite could be a promising biocompatible biomaterial for biomedical applications.

In vitro evaluation of barium titanate nanoparticle/alginate 3D scaffold for osteogenic human stem cell differentiation.

Nanomaterials can mimic properties of extracellular matrix molecules, promising great potential for scaffold composition in tissue engineering. In the present study, we investigated whether barium titanate nanoparticles (BT NP) combined with alginate polymer would provide a new cytocompatible three-dimensional (3D) scaffold to induce osteogenic stem cell differentiation. In vitro cytocompatibility and osteogenic differentiation potential were investigated using human mesenchymal stem cells (MSC). Firstly, we studied the cell viability and oxidative stress by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) thiazolyl blue tetrazolium bromide (MTT) and superoxide dismutase (SOD) assays. Overall, neither pure BT NP or BT NP/alginate 3D scaffold induced cytotoxicity. The scanning electron and atomic force microscopy revealed that BT NP/alginate 3D scaffold produced exhibited highly interconnected pores and surface nanotopography that were favorable for MSC differentiation. Von Kossa staining showed mineralization nodules and MSCs morphology changed from spindle to cuboid shape after 21 d. Finally, BMP-2 and ALP mRNA were significantly upregulated on cells grown into the BT NP/alginate 3D scaffold. Thus, the BT NP/alginate 3D scaffold showed an osteogenic differentiation induction potential, without the addition of osteogenic supplements. These results indicate that the BT NP/alginate 3D scaffold provides a cytocompatible and bioactive microenvironment for osteogenic human MSC differentiation.

Antileishmanial activity of aldonamides and N-acyl-diamine derivatives.

A number of lipophilic N-acyl-diamines and aldonamides have been synthesized and tested for their in vitro antiproliferative activity against Leishmania amazonensis and L. chagasi. Ribonamides, having one amino group, displayed good to moderate inhibition of parasite growth. The best result was obtained for compounds 10 and 15 with IC50 against L. chagasi below 5 microM.

Synthesis and Antibacterial Activity of Alkylated Diamines and Amphiphilic Amides of Quinic Acid Derivatives.

Different series of N-alkylated diamines and their derivatives condensed to quinic acid were synthesized and tested for antibacterial properties against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. The lipophilic chain and carbohydrate moiety modulate the antibacterial activity and the compounds showed a structure-activity relationship. Overall, 11 compounds displayed better activity than chloramphenicol against Gram-positive and Gram-negative bacteria. Monoalkylated amines 2a-h displayed an activity similar to that of ethambutol against Mycobacterium tuberculosis.

Synthesis and antibacterial activity of aromatic and heteroaromatic amino alcohols.

Two series of aromatic and heteroaromatic amino alcohols were synthesized from alcohols and aldehydes and evaluated for their antibacterial activities. All the octylated compounds displayed a better activity against the four bacteria tested when evaluated by the agar diffusion method and were selected for the evaluation of minimal inhibitory concentration. The best results were obtained for p-octyloxybenzyl derivatives against Staphylococcus epidermidis (minimal inhibitory concentrations = 32 µm).

Relationship between structure and antibacterial activity of lipophilic N-acyldiamines.

We report in this work the preparation and antibacterial evaluation of a series of N-monoacylated diamines against six Gram-positive and 11 Gram-negative bacteria. The results obtained showed the existence of relationship between lipophilicity and antibacterial activity of the tested compounds. The best results were obtained against Gram-positive bacteria for compounds having a 10-12 carbons alkyl chain. Compound 4e was the most active against Microccus lentus (MIC=2 microg/mL), Staphylococcus aureus ATCC 29213 (MIC=4 microg/mL) and Enterobacter aerogenes CDC 1680 (MIC=8 microg/mL).

Antibacterial activity of lipophilic fluoroquinolone derivatives.

We report in this work the antibacterial evaluation of 12 lipophilic fluoroquinolone derivatives containing diaminoalkyl side chains at C-7 position. The compounds were investigated against 15 bacterial strains including gram-negative and gram-positive species of clinical and microbiological importance. Three compounds (5, 10 and 11) were as active as or more efficient than gatifloxacin against gram-positive bacteria M. lentus. When compared with gatifloxacin compound 10 was 16 times more active. Two compounds (11 and 12) were twice more active than the reference compound against S. aureus.