Peptide nucleic acids (PNAs) control function of SARS-CoV-2 frameshifting stimulatory element trough PNA-RNA-PNA triplex formation.

The highly structured nature of the SARS-CoV-2 genome provides many promising antiviral drug targets. One particularly promising target is a -acting RNA pseudoknot found within a critical region called the frameshifting stimulatory element (FSE). In this study, peptide nucleic acids (PNAs) binding to stem 2 of FSE RNA inhibited protein translation and frameshifting, as measured by a cell-free dual luciferase assay, more effectively than PNAs binding to stem 1, stem 3, or the slippery site.

Rapid mutation detection in extracellular vesicle-DNA.

A PCR- and sequencing-free mutation detection assay facilitates cancer diagnosis and reduces over-reliance on specialized equipment. This benefit was highlighted during the pandemic when high demand for viral nucleic acid testing often sidelined mutation analysis. This shift led to substantial challenges for patients on targeted therapy in tracking mutations.

Triplex-Forming Peptide Nucleic Acid Controls Dynamic Conformations of RNA Bulges.

RNA folding is driven by the formation of double-helical segments interspaced by loops of unpaired nucleotides. Among the latter, bulges formed by one or several unpaired nucleotides are one of the most common structural motifs that play an important role in stabilizing RNA-RNA, RNA-protein, and RNA-small molecule interactions. Single-nucleotide bulges can fold in alternative structures where the unpaired nucleobase is either looped-out (flexible) in a solvent or stacked-in (intercalated) between the base pairs.

Identification of Potential Long Non-Coding RNA Candidates that Contribute to Triple-Negative Breast Cancer in Humans through Computational Approach.

Breast cancer (BC) is the most frequent malignancy identified in adult females, resulting in enormous financial losses worldwide. Owing to the heterogeneity as well as various molecular subtypes, the molecular pathways underlying carcinogenesis in various forms of BC are distinct. Therefore, the advancement of alternative therapy is required to combat the ailment.

Effects of chain length of polyethylene glycol molecular crowders on a mutant group I ribozyme lacking large peripheral module.

While current group I ribozymes use several distinct strategies to function under conditions of low Mg concentration (≤ 3 mM), a deletion mutant of the ribozyme (ΔP5 ribozyme) is virtually inactive with 3 mM Mg due to removal of the large peripheral module, P5abc, supporting the active conformation of the core module. We investigated the molecular crowding effects of synthetic polyethylene glycols (PEGs) on the activity of the ΔP5 ribozyme. Among PEG molecules with different chain lengths, PEG600 improved the activity of the ΔP5 ribozyme most effectively in the presence of 3 mM Mg.

Disposal Practices of Unused and Leftover Medicines in the Households of Dhaka Metropolis.

This fact-finding study aimed to attain an overall idea and knowledge about medicine disposal practices in Dhaka Metropolitan households. This mixed study (both quantitative and qualitative) was orchestrated to inspect the household leftover medicine disposal pattern's governing status. A cross-sectional survey was conducted following a structured questionnaire and key informant interview with a household person and in-depth interviews with the top pharmaceutical and government officials.

Mesoporous Carbon: A Versatile Material for Scientific Applications.

Mesoporous carbon is a promising material having multiple applications. It can act as a catalytic support and can be used in energy storage devices. Moreover, mesoporous carbon controls body's oral drug delivery system and adsorb poisonous metal from water and various other molecules from an aqueous solution.

An Overview on the Development of mRNA-Based Vaccines and Their Formulation Strategies for Improved Antigen Expression In Vivo.

The mRNA-based vaccine approach is a promising alternative to traditional vaccines due to its ability for prompt development, high potency, and potential for secure administration and low-cost production. Nonetheless, the application has still been limited by the instability as well as the ineffective delivery of mRNA in vivo. Current technological improvements have now mostly overcome these concerns, and manifold mRNA vaccine plans against various forms of malignancies and infectious ailments have reported inspiring outcomes in both humans and animal models.

Exploring the New Horizon of AdipoQ in Obesity-Related Alzheimer's Dementia.

Alzheimer's disease (AD) is the most common form of dementia, which causes abnormalities in learning, thinking, memory, as well as behavior. Generally, symptoms of AD develop gradually and aggravate over time, and consequently severely interfere with daily activities. Furthermore, obesity is one of the common risk factors for dementia.

Estrogen Signaling in Alzheimer's Disease: Molecular Insights and Therapeutic Targets for Alzheimer's Dementia.

Estrogens play a crucial physiological function in the brain; however, debates exist concerning the role of estrogens in Alzheimer's disease (AD). Women during pre-, peri-, or menopause periods are more susceptible for developing AD, suggesting the connection of sex factors and a decreased estrogen signaling in AD pathogenesis. Yet, the underlying mechanism of estrogen-mediated neuroprotection is unclarified and is complicated by the existence of estrogen-related factors.

Exploring the Multifunctional Neuroprotective Promise of Rasagiline Derivatives for Multi-Dysfunctional Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic, age-related, and irreversible brain disorder that typically develops slowly and gets worse over time. The potent auspicious drug candidate for the treatment of AD is supposed to perform the simultaneous modulation of several targets linked to AD. The new therapeutic approach involves drug candidates that are designed to act on multiple targets and have various pharmacological properties.

TV 3326 for Alzheimer's dementia: a novel multimodal ChE and MAO inhibitors to mitigate Alzheimer's-like neuropathology.

Objectives: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders and a well-recognized cause of dementia with ageing. In this review, we have represented the ChE and MAO inhibitory potential of TV 3326 against AD based on current scientific evidence.

Key Findings: The aetiology of AD is quite complex and not completely understood.

Effects of molecular crowding on a bimolecular group I ribozyme and its derivative that self-assembles to form ribozyme oligomers.

In the RNA world, enrichment of self-replicating RNAs would have been beneficial to their survival, amplification, and evolution. Self-assembly of RNAs may be a strategy by which they enrich themselves. We examined the effects of molecular crowding on the activity of a bimolecular group I ribozyme and its derivative that self-assembles to form ribozyme oligomers.

Oligomerization of a Bimolecular Ribozyme Modestly Rescues its Structural Defects that Disturb Interdomain Assembly to Form the Catalytic Site.

The emergence of cellular compartmentalization was a crucial step in the hypothetical RNA world and its evolution because it would not only prevent the extinction of RNA self-replication systems due to dispersion/diffusion of their components but also facilitate ribozyme reactions by molecular crowding effects. Here, we proposed and examined self-assembly of RNA components as a primitive cellular-like environment, which may have the ability to mimic cellular compartmentalization and crowding effects. We engineered a bimolecular group I ribozyme to form a one-dimensional (1D)-ribozyme assembly.

Biogenic triamine and tetraamine activate core catalytic ability of Tetrahymena group I ribozyme in the absence of its large activator module.

Group I intron ribozymes share common core elements that form a three-dimensional structure responsible for their catalytic activity. This core structure is unstable without assistance from additional factors that stabilize its tertiary structure. We examined biogenic triamine and tetraamine and also their fragments for their abilities to stabilize a structurally unstable group I ribozyme, ΔP5 ribozyme, derived from the Tetrahymena group I intron ribozyme by deleting its large activator module.

Artificial RNA Motifs Expand the Programmable Assembly between RNA Modules of a Bimolecular Ribozyme Leading to Application to RNA Nanostructure Design.

A bimolecular ribozyme consisting of a core ribozyme (ΔP5 RNA) and an activator module (P5abc RNA) has been used as a platform to design assembled RNA nanostructures. The tight and specific assembly between the P5abc and ΔP5 modules depends on two sets of intermodule interactions. The interface between P5abc and ΔP5 must be controlled when designing RNA nanostructures.