An Atomic Level Investigation of Sodium Ions Regulating Agonist and Antagonist Binding in the Active Site of a Novel Target 5HT2BR Against Drug-Resistant Epilepsy.

The study investigates the movement of sodium ions inside the ligand-binding pocket of the class-A GPCR serotonin receptor (5HT2BR), a primary target for modern drugs. The available PDBs are mutant chimeras, so a 3D structure is modeled and validated by structural similarity (84.05%), Ramachandran favorable residues (93.01%), and clash score. Using MD simulations (500 ns), the ion active site is tracked in the presence and absence of ions and ligands. The ions enter the active site along helices III, VI, and VII, and the primary residue (ASP3.32) interacts with ions via H-bond (stronger- ~2.4 Å). The radial distribution function around ASP3.32 rises promptly at intermediate distances (2 Å < r < 4 Å), suggesting a higher probability of finding sodium ions at these distances. The ions stabilize the receptor at a better RMSD and promote stronger interactions (3-H-bonds, 1-π-bond~3.35 Å) with the agonist, and not the antagonist (no H-bond). Simulating unrestrained ligands further confirms this pattern, suggesting that ions might promote agonist binding but not be a prerequisite for antagonist action. The study highlights the mechanistic evaluation of sodium ions mobility in 5HT2BR modulation and ligand binding, showing potential in drug development.

DNA dyes: toxicity, remediation strategies and alternatives.

Release of untreated effluent from processing or manufacturing industries and other commercial premises into water bodies is a major threat to environment and human health. In this regard, the effluent generated from laboratories and other research facilities is of great concern. Among other harmful chemicals, the effluent is rich in toxic organic dyes, which get exposed to the environment and pose serious health risk. The dyes used in nucleic acid analysis specially the DNA dyes are known for their teratogenicity and mutagenic potential, which mainly depends upon the organism and circumstances under which it is exposed. Among animals and humans, exposure to theses dyes may lead to irritation in mouth, eyes and respiratory tract and many other possible effects which are yet to be explored. To overcome these problems, dyes present in the effluents from laboratories must be degraded to non-toxic forms. Various strategies have been proposed and investigated for degradation and remediation of contaminated laboratory effluent. As a modern and cost-effective technique, biodegradation using microbes and plants is potentially eco-friendly and sustainable technique for detoxifying these dyes. In this article, we have discussed and reviewed the structure, properties and toxicity profile of prominent nucleic acid dyes, along with the strategies of remediation of laboratory effluents contaminated with these dyes. In addition, we have also discussed the feasibility and limitations of these remediation strategies and identified research gaps that can help researchers to explore more effective solutions to manage this area of great concern. We have also reviewed various less toxic alternatives of these common as safer options of these dyes.

Hb Rush (HBB: c.304G>C): A Rare Variant Hemoglobin Mimicking the Hb S (HBB: c.20A>T) Variant on High Performance Liquid Chromatography.

High performance liquid chromatography (HPLC) is a useful and rapid tool in the evaluation of hemoglobin (Hb) disorders that include thalassemia and various hemoglobinopathies. Most of the techniques or programs used in automated testing platforms are customized to identify the common variants seen in that particular region. At times, variant Hbs may be identified which are not commonly seen in the local population. This may cause diagnostic dilemma and may require further studies for definitive characterization. We present a patient with Hb Rush (HBB: c.304G>C), a rare unstable Hb variant eluting in the Hb S (HBB: c.20A>T) window on HPLC.