Exposure to Tetrabutylammonium Bromide Impairs Cranial Neural Crest Specification, Neurogenic Program, and Brain Morphogenesis.

Tetrabutylammonium bromide (TBAB) is a widely used industrial reagent and is commonly found in our aquatic ecosystem as an industrial byproduct. In humans, the ingestion of TBAB causes severe neurological impairments and disorders such as vertigo, hallucinations, and delirium. Yet, the extent of environmental risk and TBAB toxicity to human health is poorly understood. In this study, we aim to determine the developmental toxicity of TBAB using zebrafish embryos as a model and provide novel insights into the mechanism of action of such chemicals on neurodevelopment and the overall embryonic program. Our results show that exposure to TBAB results in impaired development of the brain, inner ear, and pharyngeal skeletal elements in the zebrafish embryo. TBAB treatment resulted in aberrations in the specification of the neural crest precursors, hindbrain segmentation, and otic neurogenesis. TBAB treatment also induced a surge in apoptosis in the head, tail, and trunk regions of the developing embryo. Long-term TBAB exposure resulted in cardiac edema and craniofacial defects. Further, in silico molecular docking analysis indicated that TBAB binds to AMPA receptors and modulates neural developmental genes such as olfactomedin and acetylcholinesterase in the embryonic brain. To summarize, our study highlights the novel effects of TBAB on embryonic brain formation and segmentation, ear morphogenesis, and craniofacial skeletal development.

Ferromagnetism in Defected TMD (MoX2, X = S, Se) Monolayer and Its Sustainability under O2, O3, and H2O Gas Exposure: DFT Study.

Spin-polarized density-functional theory (DFT) has been employed to study the effects of atmospheric gases on the electronic and magnetic properties of a defective transition-metal dichalcogenide (TMD) monolayer, MoX2 with X = S or Se. This study focuses on three single vacancies: (i) molybdenum "VMo"; (ii) chalcogenide "VX"; and (iii) di-chalcogenide "VX2". Five different samples of sizes ranging from 4 × 4 to 8 × 8 primitive cells (PCs) were considered in order to assess the effect of vacancy-vacancy interaction. The results showed that all defected samples were paramagnetic semiconductors, except in the case of VMo in MoSe2, which yielded a magnetic moment of 3.99 µB that was independent of the sample size. Moreover, the samples of MoSe2 with VMo and sizes of 4 × 4 and 5 × 5 PCs exhibited half-metallicity, where the spin-up state becomes conductive and is predominantly composed of dxy and dz2 orbital mixing attributed to Mo atoms located in the neighborhood of VMo. The requirement for the establishment of half-metallicity is confirmed to be the provision of ferromagnetic-coupling (FMC) interactions between localized magnetic moments (such as VMo). The critical distance for the existence of FMC is estimated to be dc≅ 16 Å, which allows small sample sizes in MoSe2 to exhibit half-metallicity while the FMC represents the ground state. The adsorption of atmospheric gases (H2O, O2, O3) can drastically change the electronic and magnetic properties, for instance, it can demolish the half-metallicity characteristics. Hence, the maintenance of half-metallicity requires keeping the samples isolated from the atmosphere. We benchmarked our theoretical results with the available data in the literature throughout our study. The conditions that govern the appearance/disappearance of half-metallicity are of great relevance for spintronic device applications.

RUFY3 links Arl8b and JIP4-Dynein complex to regulate lysosome size and positioning.

The bidirectional movement of lysosomes on microtubule tracks regulates their whole-cell spatial arrangement. Arl8b, a small GTP-binding (G) protein, promotes lysosome anterograde trafficking mediated by kinesin-1. Herein, we report an Arl8b effector, RUFY3, which regulates the retrograde transport of lysosomes. We show that RUFY3 interacts with the JIP4-dynein-dynactin complex and facilitates Arl8b association with the retrograde motor complex. Accordingly, RUFY3 knockdown disrupts the positioning of Arl8b-positive endosomes and reduces Arl8b colocalization with Rab7-marked late endosomal compartments. Moreover, we find that RUFY3 regulates nutrient-dependent lysosome distribution, although autophagosome-lysosome fusion and autophagic cargo degradation are not impaired upon RUFY3 depletion. Interestingly, lysosome size is significantly reduced in RUFY3 depleted cells, which could be rescued by inhibition of the lysosome reformation regulatory factor PIKFYVE. These findings suggest a model in which the perinuclear cloud arrangement of lysosomes regulates both the positioning and size of these proteolytic compartments.

A drift on liposomes to proliposomes: recent advances and promising approaches.

Liposomes are nano-structured vesicles, made up of phospholipids that provide active ingredients at the site of action at a predetermined rate and add the advantage of the sustained-release formulation. Liposomes have stability issues that tend to agglomerate and fuse upon storage, which reflects their drawback. Hence to overcome the aggregation, fusion, hydrolysis, and/or oxidation problems associated with liposomes a new technology named Proliposomes has been introduced. Proliposomes are defined as carbohydrate carriers coated with phospholipids, which upon addition of water generate liposomes. The objective of the review is to cover the concept of proliposomes for pulmonary or alveolar delivery of drugs and compare it with that of liposomes; highlight the methods used for preparations along with the characterization parameters. This is the first systematic review that covers the categorization of liposomes, characteristic methods, and recent examples of drugs from 2015 to 2021, supplied in form of proliposomes to the macrophages as well as others and offers an advantage over the free drug by offering a prolonged drug release and sufficient bioavailability in addition to overcome the stability issues related to liposomes. Since this is a very new technology and many scientists are continuously working in this field to make the drug available for clinical trials and ultimately in the market for the targeted delivery of drugs with better storage life.HIGHLIGHTSProliposomes as an alternative to overwhelm the stability and storage-related issues of liposomes.Anhydrous carbohydrate carriers are utilized for proliposomal preparation.Inhaled delivery of drugs as solid lipid nanoparticles offers a significant impact on pulmonary tract infections, particularly in cystic fibrosis.Size of liposomes attained after proliposome hydrolysis is critical for drug delivery via respiration.

Binary adsorption of [Pb(II) + Co(II)] from aqueous solution using thiolated saw dust.

Technology advancement has contributed to an increase in industrial activities, resulting in the introduction of metal ions into water resources at concentrations well above the WHO limits. Heavy metals are highly toxic and carcinogenic; they usually occur as multicomponent mixtures in the aquatic environment. In the present study, batch experiments have been conducted to study the dependence of varying concentration, time, pH and temperature on the uptake of Pb(II) as a pure component under equilibrium conditions using thiolated saw dust. Saw dust has been chemically modified with thioglycolic acid and characterised using proximate and FTIR analyses, the degree of thiolation has also been determined. To determine the effect of the presence of Co(II) ions on the uptake of Pb(II) ions, batch experiments for [Pb(II) + Co(II)] mixture have been carried out for concentration ratios of 1:0, 1:1, 1:2, 1:3, 1:4 of Pb:Co at pH 5 and data has been interpreted using Langmuir competitive isotherm, which shows that adsorption of Pb(II) has been suppressed by the presence of Co(II) ions in the binary solution, hence the adsorption process is antagonistic in nature. The study also indicates the possibility of simultaneous removal of both metal ions using low cost bioadsorbent, which is economical especially for application in small-scale industries.

Engagement of phytoestrogens in breast cancer suppression: Structural classification and mechanistic approach.

Cancer is the world's devastating disease, and breast cancer is the most common reason for the death of women worldwide. Many synthetic drugs and medications are provided with their beneficial actions, but all of these have side effects and resistance problems. Natural remedies are coming forward to overcome the disadvantages of synthetic drugs. Among the natural categories, phytoestrogens having a structural similarity of mammalian oestradiol proves its benefit with various mechanisms not only in the treatment of breast cancer but even to prevent the occurrence of postmenopausal symptoms. Phytoestrogens are plant-derived compounds that were utilized in ancient medications and traditional knowledge for its sex hormone properties. Phytoestrogens exert pleiotropic effects on cellular signalling and show effects on estrogen-dependent diseases. However, because of activation/inhibition of steroid hormonal receptor ER-α or ER-ß, these compounds induce or inhibit steroid hormonal (estrogen) action and, therefore, have the potential to disrupt hormone (estrogen) signalling pathway. In this review, we have discussed and summarize the effect of certain phytoestrogens and their possible mechanisms that can substantiate advantageous benefits for the treatment of post-menopausal symptoms as well as for breast cancer.

Tetrazoles as anticancer agents: A review on synthetic strategies, mechanism of action and SAR studies.

Cancer is a leading cause of death worldwide. Even after the availability of numerous drugs and treatments in the market, scientists and researchers are focusing on new therapies because of their resistance and toxicity issues. The newly synthesized drug candidates are able to demonstrate in vitro activity but are unable to reach clinical trials due to their rapid metabolism and low bioavailability. Therefore there is an imperative requisite to expand novel anticancer negotiators with tremendous activity as well as in vivo efficacy. Tetrazole is a promising pharmacophore which is metabolically more stable and acts as a bioisosteric analogue for many functional groups. Tetrazole fragment is often castoff with other pharmacophores in the expansion of novel anticancer drugs. This is the first systematic review that emphasizes on contemporary strategies used for the inclusion of tetrazole moiety, mechanistic targets along with comprehensive structural activity relationship studies to provide perspective into the rational design of high-efficiency tetrazole-based anticancer drug candidates.

Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs.

BACKGROUND: The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. OBJECTIVES: The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. MATERIAL AND METHODS: The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. RESULTS: All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). CONCLUSIONS: Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.