Nanomedicine at the Pulmonary Frontier: Immune-Centric Approaches for Respiratory Disease Treatment.

Respiratory diseases (RD) are a group of common ailments with a rapidly increasing global prevalence, posing a significant threat to humanity, especially the elderly population, and imposing a substantial burden on society and the economy. RD represents an unmet medical need that requires the development of viable pharmacotherapies. While various promising strategies have been devised to advance potential treatments for RD, their implementation has been hindered by difficulties in drug delivery, particularly in critically ill patients. Nanotechnology offers innovative solutions for delivering medications to the inflamed organ sites, such as the lungs. Although this approach is enticing, delivering nanomedicine to the lungs presents complex challenges that require sophisticated techniques. In this context, we review the potential of novel nanomedicine-based immunomodulatory strategies that could offer therapeutic benefits in managing this pressing health condition.

Synthesis, Reactions, and Antioxidant Properties of Bis(3-amino-1-hydroxybenzyl)diselenide.

Bis(3-amino-1-hydroxybenzyl)diselenide containing two ortho groups was synthesized from 7-nitro-3H-2,1-benzoxaselenole and in situ generated sodium benzene tellurolate (PhTeNa). One-pot synthesis of 1,3-benzoselenazoles was achieved from bis(3-amino-1-hydroxybenzyl)diselenide and aryl aldehydes using acetic acid as a catalyst. The X-ray crystal structure of chloro-substituted benzoselenazole revealed a planar structure with T-shaped geometry around the Se atom. Both natural bond orbital and atoms in molecules calculations confirmed the presence of secondary Se···H interactions in bis(3-amino-1-hydroxybenzyl)diselenide and Se···O interactions in benzoselenazoles, respectively. The glutathione peroxidase (GPx)-like antioxidant activities of all compounds were evaluated using a thiophenol assay. Bis(3-amino-1-hydroxybenzyl)diselenide and benzoselenazoles showed better GPx-like activity compared to that of the diphenyl diselenide and ebselen, used as references, respectively. Based on 77Se{1H} NMR spectroscopy, a catalytic cycle for bis(3-amino-1-hydroxybenzyl)diselenide using thiophenol and hydrogen peroxide was proposed involving selenol, selenosulfide, and selenenic acid as intermediates. The potency of all GPx mimics was confirmed by their in vitro antibacterial properties against the biofilm formation of Bacillus subtilis and Pseudomonas aeruginosa. Additionally, molecular docking studies were used to evaluate the in silico interactions between the active sites of the TsaA and LasR-based proteins found in Bacillus subtilis and Pseudomonas aeruginosa.

Blood-brain barrier: emerging trends on transport models and new-age strategies for therapeutics intervention against neurological disorders.

The integrity of the blood-brain barrier (BBB) is essential for normal central nervous system (CNS) functioning. Considering the significance of BBB in maintaining homeostasis and the neural environment, we aim to provide an overview of significant aspects of BBB. Worldwide, the treatment of neurological diseases caused by BBB disruption has been a major challenge. BBB also restricts entry of neuro-therapeutic drugs and hinders treatment modalities. Hence, currently nanotechnology-based approaches are being explored on large scale as alternatives to conventional methodologies. It is necessary to investigate the in-depth characteristic features of BBB to facilitate the discovery of novel drugs that can successfully cross the barrier and target the disease effectively. It is imperative to discover novel strategies to treat life-threatening CNS diseases in humans. Therefore, insights regarding building blocks of BBB, activation of immune response on breach of this barrier, and various autoimmune neurological disorders caused due to BBB dysfunction are discussed. Further, special emphasis is given on delineating BBB disruption leading to CNS disorders. Moreover, various mechanisms of transport pathways across BBB, several novel strategies, and alternative routes by which drugs can be properly delivered into CNS are also discussed.

Development of magnetic nanoparticle assisted aptamer-quantum dot based biosensor for the detection of Escherichia coli in water samples.

The contamination of food and potable water with microorganisms may cause food-borne and water-borne diseases. The common contaminants include Escherichia coli (E. coli), Salmonella sp. etc. The conventional methods for monitoring the water quality for the presence of bacterial contaminants are time-consuming, expensive, and not suitable for rapid on-spot detection in field conditions. In the current study, super paramagnetic iron oxide nanoparticles (SPIONs) were synthesized and conjugated with E. coli specific Aptamer I to detect E. coli cells qualitatively as well as quantitatively. The sludge consisting of E. coli- SPION complex was separated via magnetic separation. The presence of E. coli cells was confirmed with the help of standard techniques and confocal laser scanning microscopy (CLSM) employing Aptamer II conjugated CdTe-MPA quantum dots (QDs). Finally, an ATmega 328P prototype biosensor based on Aptamer II conjugated CdTe MPA QDs exhibited quantitative and qualitative abilities to detect E.coli. This prototype biosensor can even detect low bacterial counts (up to 1 × 102 cfu) with the help of a photodiode and plano-convex lens. Further, the prototype biosensor made up of ultraviolet light-emitting diode (UV LED), liquid crystal display (LCD) and ATmega328Pmicrocontroller offers on-spot detection of E.coli in water samples with high resolution and sensitivity. Similarly, this in-house developed prototype biosensor can also be utilized to detect bacterial contamination in food samples.

RNA thermometers and other regulatory elements: Diversity and importance in bacterial pathogenesis.

Survival of microorganisms depends to a large extent on environmental conditions and the occupied host. By adopting specific strategies, microorganisms can thrive in the surrounding environment and, at the same time, preserve their viability. Evading the host defenses requires several mechanisms compatible with the host survival which include the production of RNA thermometers to regulate the expression of genes responsible for heat or cold shock as well as of those involved in virulence. Microorganisms have developed a variety of molecules in response to the environmental changes in temperature and even more specifically to the host they invade. Among all, RNA-based regulatory mechanisms are the most common ones, highlighting the importance of such molecules in gene expression control and novel drug development by suitable structure-based alterations. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA in Disease and Development > RNA in Disease RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems.

Carbon Based Nanodots in Early Diagnosis of Cancer.

Detection of cancer at an early stage is one of the principal factors associated with successful treatment outcome. However, current diagnostic methods are not capable of making sensitive and robust cancer diagnosis. Nanotechnology based products exhibit unique physical, optical and electrical properties that can be useful in diagnosis. These nanotech-enabled diagnostic representatives have proved to be generally more capable and consistent; as they selectively accumulated in the tumor site due to their miniscule size. This article rotates around the conventional imaging techniques, the use of carbon based nanodots viz Carbon Quantum Dots (CQDs), Graphene Quantum Dots (GQDs), Nanodiamonds, Fullerene, and Carbon Nanotubes that have been synthesized in recent years, along with the discovery of a wide range of biomarkers to identify cancer at early stage. Early detection of cancer using nanoconstructs is anticipated to be a distinct reality in the coming years.

Fluorescence and Förster resonance energy transfer investigations on DNA oligonucleotide and PAMAM dendrimer packing interactions in dendriplexes.

Considering the importance of short oligonucleotide packing in dendriplex-mediated gene delivery, a direct insight into the 14-mer oligonucleotide and dendrimer interactions using fluorescence and FRET techniques is the focus of this study. Fluorometric titrations of various fluorophore-tagged oligonucleotides with the first three PAMAM dendrimer generations showed a decrease in the fluorescence intensity with two break points, namely Z and Z, for each titration. The first break point for each dendrimer was identical to the neutralization point observed by basic biophysical studies for the corresponding dendrimer generations. Additionally, FRET studies on dual tagged oligonucleotide (DFT) molecules revealed a third break point at the charge ratio (Z) where there was the highest fluorescence energy transfer from the donor to the acceptor fluorophores. Altogether, dendriplex formation was considered to take place via three steps with an increase in the dendrimer concentration, where initially there was monomeric complexation at the neutralization point (Z) followed by loosely held molecular aggregation of the dendrimer (Z). In the final step, dendrimer molecular aggregates were held tightly together for the closest possible packing of the oligonucleotide molecules onto their surface. The effective molecular packing is identified by the highest FRET intensity for the dendrimer of generation 2 at a charge ratio of 0.34 (Z±).

Bio-inspired synthesis of microporous bioactive glass-ceramic using CT-DNA as a template.

We report, for the first time, bio-inspired synthesis of a bioactive glass-ceramic with superior textural properties in atmospheric conditions using CT-DNA as template. The phase composition, structure, morphology, and textural properties of the bioactive glass sample were evaluated with various analytical techniques before and after in vitro tests. The BET surface area analysis of the obtained glass-ceramic sample reveals that it possesses a high surface area with a range of (micro- to meso-) pore sizes. The TEM analysis of the glass-ceramic phase indicates that the amorphous phase consists of spherical particles, whereas the crystalline phase is found to have needle-like shape. In the glass-ceramic, we find a new type of crystalline phase (Na0.11Ca0.89)(P0.11Si0.89)O3, which is different from the earlier observation on 45S5® glass-ceramic sample. The accelerated in vitro bioactivity of the glass-ceramic is evidenced based on the hydroxyl carbonate apatite (HCA) layer formation on the glass-ceramic surface after immersing the bioglass sample in simulated body fluid (SBF), by FTIR, SEM and EDX analysis. Additionally, the ion release kinetics of the bioglass sample in SBF is followed by ICP-AES with simultaneous pH measurements. The in vitro cytotoxicity experiments on the glass-ceramic sample using osteosarcoma cells by following the MTT assay method indicate that the sample has good biocompatibility and may serve as an effective biomaterial for bone tissue engineering.