Leveraging a Separation of States Method for Relative Binding Free Energy Calculations in Systems with Trapped Waters.

Methods for calculating the relative binding free energy (RBFE) between ligands to a target protein are gaining importance in the structure-based drug discovery domain, especially as methodological advances and automation improve accuracy and ease of use. In an RBFE calculation, the difference between the binding affinities of two ligands to a protein is calculated by transforming one ligand into another, in the protein-ligand complex, and in solvent. Alchemical binding free energy calculations are often used for such ligand transformations.

Micellar "Click" Nanoreactors: Spiking Pluronic-Based Micelles with Polymeric Ligands.

In recent years, the development of nanoreactors, such as micellar nanoreactors (MNRs) for catalytic transformations, has gained significant attention due to their potential in enhancing reaction rates, selectivity, efficiency, and, as importantly, the ability to conduct organic chemistry in aqueous solutions. Among these, the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction represents a pivotal transformation and is widely used in the synthesis of bioconjugates, pharmaceuticals, and advanced materials. This study aims toward advancing our understanding of the design and utilization of polymeric amphiphiles containing tris-triazole ligands as an integral element for CuAAC reactions within MNRs.

Caregiving Intensity, Duration, and Subjective Financial Well-Being Among Rural Informal Caregivers of Older Adults with Chronic Illnesses or Disabilities.

Introduction: Rural informal caregivers (IC) experience major financial and economic constraints in caring for their older family members. Rurality combined with increased caregiving demands and intensity, poor economic opportunities, and limited financial resources and policies create multiple financial stressors and can lead to poor financial well-being. A cross-sectional survey was conducted to understand how caregiving demands, intensity, and duration impact the subjective financial well-being of rural caregivers of older adults.

Advanced drug delivery strategies for diabetic retinopathy: current therapeutic advancement, and delivery methods overcoming barriers, and experimental modalities.

Introduction: Diabetic retinopathy, a significant trigger for blindness among working age individuals with diabetes, poses a substantial global health challenge. Understanding its underlying mechanisms is pivotal for developing effective treatments. Current treatment options, such as anti-VEGF agents, corticosteroids, laser photocoagulation, and vitreous surgery, have their limitations, prompting the exploration of innovative approaches like nanocapsules based drug-delivery systems.

Exploring delivery systems for targeted nanotechnology-based gene therapy in the inner ear.

Hearing loss places a significant burden on our aging population. However, there has only been limited progress in developing therapeutic techniques to effectively mediate this condition. This review will outline several of the most commonly utilized practices for the treatment of sensorineural hearing loss before exploring more novel techniques currently being investigated via both and research.

Pediatric Advanced Life Support Tape for Indian Children.

Objective: To design a specific advanced life support (ALS) tape based on recent Indian multicenter height/length and weight data to accurately estimate the weight from the recumbent length.

Methods: We designed the new ALS tape by matching the median weights to median heights/lengths from the recently published Indian multicenter growth data, maintaining the same color codes as the Broselow tape. The accuracy of weight estimation for the newly designed ALS tape was validated and compared with the Broselow estimated weights at a tertiary care hospital.

Polymer-Based Nanoparticles with Probucol and Lithocholic Acid: A Novel Therapeutic Approach for Oxidative Stress-Induced Retinopathies.

Oxidative stress is pivotal in retinal disease progression, causing dysfunction in various retinal components. An effective antioxidant, such as probucol (PB), is vital to counteract oxidative stress and emerges as a potential candidate for treating retinal degeneration. However, the challenges associated with delivering lipophilic drugs such as PB to the posterior segment of the eye, specifically targeting photoreceptor cells, necessitate innovative solutions.

Polymer-Based Nanoparticles for Inner Ear Targeted Trans Differentiation Gene Therapy.

Hearing loss is a significant disability that often goes under recognised, largely due to poor identification, prevention, and treatment. Steps are being made to amend these pitfalls in the investigation of hearing loss, however, the development of a cure to reverse advanced forms remains distant. This review details some current advances in the treatment of hearing loss, with a particular focus on genetic-based nanotechnology and how it may provide a useful avenue for further research.

Probucol-bile acid nanoparticles: a novel approach and promising solution to prevent cellular oxidative stress in sensorineural hearing loss.

The use of antioxidants could thus prove an effective medication to prevent or facilitate recovery from oxidative stress-induced sensorineural hearing loss (SNHL). One promising strategy to prevent SNHL is developing probucol (PB)-based nanoparticles using encapsulation technology and administering them to the inner ear via the established intratympanic route. The preclinical, clinical and epidemiological studies support that PB is a proven antioxidant that could effectively prevent oxidative stress in different study models.

Probucol-Ursodeoxycholic Acid Otic Formulations: Stability and In Vitro Assessments for Hearing Loss Treatment.

Targeted drug delivery is an ongoing aspect of scientific research that is expanding through the design of micro- and nanoparticles. In this paper, we focus on spray dried microparticles as carriers for a repurposed lipophilic antioxidant (probucol). We characterise the microparticles and quantify probucol prior to assessing cytotoxicity on both control and cisplatin treated hair cells (known as House Ear Institute-Organ of Corti 1; HEI-OC1).

Asymmetric Cluster-Based Measures for Comparative Phylogenetics.

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Enhancing fraud detection in banking by integration of graph databases with machine learning.

The banking sector's shift from traditional physical locations to digital channels has offered customers unprecedented convenience and increased the risk of fraud for customers and institutions alike. In this study, we discuss the pressing need for robust fraud detection & prevention systems in the context of evolving technological environments. We introduce a graph-based machine learning model that is specifically designed to detect fraudulent activity in various types of banking operations, such as credit card transactions, debit card transactions, and online banking transactions.

Biotechnological Effects of Advanced Smart-Bile Acid Cyclodextrin-Based Nanogels for Ear Delivery and Treatment of Hearing Loss.

Inner ear delivery requires safe and effective drug delivery vehicles incorporating high-viscosity formulations with permeation enhancers. This study designs novel thermoresponsive-smart polymer-bile acid and cyclodextrin-based nanogels for inner ear delivery. Nanogels are examined for their rheological and physical properties.

Probucol-bile acid based nanoparticles protect auditory cells from oxidative stress: an study.

Excessive free radicals contribute to oxidative stress and mitochondrial dysfunction in sensorineural hearing loss (SNHL). The antioxidant probucol holds promise, but its limited bioavailability and inner ear barriers hinder effective SNHL treatment. We addressed this by developing probucol-loaded nanoparticles with polymers and lithocholic acid and tested them on House Ear Institute-Organ of Corti cells.

Cecal volvulus following appendectomy in a teenage patient: A case report.

Unlabelled: Patients mimicking appendicitis symptoms in a rural setting or those post-appendectomy, indicating cecal volvulus, should always be considered. Swift action can prevent catastrophic consequences.

Abstract: We present a case of a 14-year-old female who initially underwent open appendectomy for acute appendicitis and subsequently experienced symptoms of abdominal distention, vomiting, and fever.

Synergistic Cytotoxicity of Extracts of Chaga Mushroom and Microalgae against Mammalian Cancer Cells In Vitro.

Chaga mushroom () contains bioactive metabolites and has been used to treat various ailments, including cancer. Similarly, marine microalgae are considered a sustainable food supplement with anticancer and antioxidant properties. This study investigated the cytotoxicity of different extracts prepared from and microalgae using cultured human and canine cancer cell lines (MCF-7, HepG2, HOS, D-17, and DH-82).

Bile Acid Application in Cell-Targeting for Molecular Receptors in Relation to Hearing: A Comprehensive Review.

Bile acids play important roles in the human body, and changes in their pool can be used as markers for various liver pathologies. In addition to their functional effects in modulating inflammatory responses and cellular survivability, the unconjugated or conjugated, secondary, or primary nature of bile acids accounts for their various ligand effects. The common hydrophilic bile acids have been used successfully as local treatment to resolve drug-induced cell damage or to ameliorate hearing loss.

Novel polysaccharides-bile acid-cyclodextrin gel systems and effects on cellular viability and bioenergetic parameters.

The novel hydrogel systems made from sodium alginate, pectin, beta-cyclodextrin and deoxycholic acid (DCA) were proposed as potential drug-delivery matrices. To ensure biocompatibility, rheological parameters were examined and hydrogels' effects on bioenergetic parameters and cellular viability on murine hepatic, and muscle and pancreatic beta cells. All hydrogels show non-Newtonian, shear thinning behavior.

The effect of deoxycholic acid-based hydrogels on hepatic, muscle and pancreatic beta cells.

The aim of this study is to test the biocompatibility of hydrogels with polysaccharides and bile acids on three murine cell lines. Novel hydrogels containing poloxamer 407, polysaccharides (starch, pectin, acacia, carboxymethyl and methyl 2-hydroxyethyl cellulose) and deoxycholic acid were prepared using cold method, sterilized and used in biological assays to determine effects on hepatic, muscle, and pancreatic beta cells. Hydrogels with deoxycholic acid had tissue-depending effects on cellular survival and bioenergetics, resulting in the best cellular viability and bioenergetics within pancreatic beta cells.

Chaga mushroom triterpenoids as adjuncts to minimally invasive cancer therapies: A review.

Cancer has become the second leading cause of death in the world. Integrative cancer therapy management is continuously evolving to enhance treatment outcomes. Chaga mushroom () is a parasitic fungus acclaimed to contain pharmaceutical and nutraceutical value in the fight against cancer.

Polymeric architecture as a tool for controlling the reactivity of palladium(II) loaded nanoreactors.

Self-assembled systems, like polymeric micelles, have become great facilitators for conducting organic reactions in aqueous media due to their broad potential applications in green chemistry and biomedical applications. Massive strides have been taken to improve the reaction scope of such systems, enabling them to perform bioorthogonal reactions for prodrug therapy. Considering these significant advancements, we sought to study the relationships between the architecture of the amphiphiles and the reactivity of their Pd loaded micellar nanoreactors in conducting depropargylation reactions.

Influence of poly-L-ornithine-bile acid nano hydrogels on cellular bioactivity and potential pharmacological applications.

Cellular bioactivity and pathophysiological changes associated with chronic disorders are considered pivotal detrimental factors when developing novel formulations for biomedical applications. This paper investigates the use of bile acids and synthetic polypeptide poly-L-ornithine (PLO) in formulations and their impacts on a variety of cell lines, with a particular focus on their cellular bioactivity. The hepatic cell line was the most negatively affected by the presence of PLO, while the muscle and beta-pancreatic cell lines did not show as profound of a negative impact of PLO on cellular viability.